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The  CONTEMPO Registry Study: A Complement to INSPIRE

As evidenced by the passing of the 21st Century Cures Act, regulators and policy makers have recently highlighted the benefits and utility of Real-World Evidence (RWE) as it pertains to the Food and Drug Administration (FDA) regulatory decision-making for medical devices. RWE is derived from Real World Data (RWD) collected outside of a traditional clinical trial and includes sources such as patient registries. InVivo is committed to providing regulatory agencies with a comprehensive benchmark comparator dataset using RWE to help support the assessment of the safety and probable benefit of its Neuro-Spinal Scaffold™.

The CONTEMPO Registry Study will utilize several large, high-quality spinal cord injury (SCI) registries that have formed the basis of dozens of high-impact, peer-reviewed publications. To the extent possible, the CONTEMPO Registry Study will apply similar inclusion/exclusion criteria to INSPIRE in order to identify appropriate patients to include into a well-matched benchmark comparator group.  Furthermore, the study will only include patients injured since 2006 in order to minimize the impacts of any temporal changes in standard of care or rehabilitation when compared to INSPIRE study data. We expect that the CONTEMPO Registry Study will provide a robust characterization of the contemporary natural history of traumatic, complete, thoracic spinal cord injury.

We are thrilled to announce that data from the Christopher & Dana Reeve Foundation North American Clinical Trials Network (NACTN) Registry will be included in the CONTEMPO Registry Study. The NACTN Registry collects extensive acute care data that will allow for close matching of registry patient characteristics with INSPIRE inclusion and exclusion criteria.

Previously, InVivo had communicated that it was considering adding a Benchmark Arm to the INSPIRE Study by gathering retrospective data from patients that presented at INSPIRE sites since 2016 but were not implanted with the Neuro-Spinal Scaffold. Given the comprehensiveness and strength of the data available in the NACTN Registry, InVivo has decided not to move forward with the Benchmark Arm.  The company believes that the CONTEMPO Registry Study will not only provide superior comparator benchmarks using prospectively gathered data but will also avoid the operational complexities and cost of a Benchmark Arm.

Since the CONTEMPO Registry Study will involve analysis of existing registries, we do not believe that it will affect any of our communicated timelines for the INSPIRE Study.  We anticipate full enrollment in the INSPIRE Study in Q3 2017 with full HDE submission of the final module of our HDE application (including the results of the CONTEMPO Registry Study) in early 2018. We believe the combined information in the INSPIRE study and the CONTEMPO Registry Study will provide a rigorous body of evidence for the demonstration of safety and probable benefit as required by the HDE approval process.

I look forward to updating you on our progress regarding this landmark clinical program.

Mark Perrin
CEO & Chairman
May 30, 2017

Safe Harbor Statement
Any statements contained in this document that do not describe historical facts may constitute forward-looking statements within the meaning of the federal securities laws. These statements can be identified by words such as “believe,” “anticipate,” “intend,” “estimate,” “will,” “may,” “should,” “expect,” “designed to,” “potentially,” and similar expressions, and include statements regarding the safety and effectiveness of the Neuro-Spinal Scaffold and the progress of the clinical program. Any forward-looking statements contained herein are based on current expectations, and are subject to a number of risks and uncertainties. Factors that could cause actual future results to differ materially from current expectations include, but are not limited to, risks and uncertainties relating to the company’s ability to successfully open additional clinical sites for enrollment and to enroll additional patients; the timing of the Institutional Review Board process; the company’s ability to complete The INSPIRE Study, submit an HDE application, and receive regulatory approval for the Neuro-Spinal Scaffold, the company’s ability to commercialize its products; the company’s ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the company’s products and technology in connection with the treatment of spinal cord injuries; the availability of substantial additional funding for the company to continue its operations and to conduct research and development, clinical studies and future product commercialization; and other risks associated with the company’s business, research, product development, regulatory approval, marketing and distribution plans and strategies identified and described in more detail in the company’s Quarterly Report of the three months ended March 31, 2017, and its other filings with the SEC, including the company’s Form 10-Qs and current reports on Form 8-K. The company does not undertake to update these forward-looking statements.

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Cervical Spinal Cord Injury: Higher Risk/Higher Reward - March 23 2017

Cervical Spinal Cord Injury: Higher Risk/Higher Reward – March 23 2017

We at InVivo are very excited to have announced that Health Canada has approved the company’s Investigational Testing Authorization application to commence a clinical study in patients with acute, complete (AIS A) cervical spinal cord injuries in Canada. These patients are the most severely injured of all SCI patients and any neurological improvement could make a significant difference in their quality of life. As compared to the thoracic spinal cord, the cervical spinal cord represents a region of higher risk and higher potential reward, since each level of this region has substantial functional impact.

The most frequently used clinical instrument to assess spinal cord injuries is the International Standard for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam. To understand the key differences between our newly-initiated cervical study and our ongoing thoracic INSPIRE study, it is helpful to understand how motor function is assessed in this exam. The most recent version of the exam can be found here: http://asia-spinalinjury.org/wp-content/uploads/2016/02/International_Stds_Diagram_Worksheet.pdf.

In the ongoing INSPIRE study, we are enrolling patients with neurologically complete (AIS A) paralysis at thoracic levels T2-T12/L1.  Perhaps surprisingly, the ISNCSCI exam doesn’t include evaluation of motor function for any of these thoracic levels. This is because the muscles innervated by the thoracic spinal cord, such as the abdominals, are clinically difficult to evaluate. The muscles of the lower limbs can be easily evaluated and are innervated by the lumbar and sacral spinal cord, which are below the thoracic region. For a patient with a T3 level injury, the closest region of the spinal cord that is evaluated for motor function in the ISNCSCI exam is at the L2 level, which is located about 7 inches away on the adult spinal cord. That is a lot of spinal cord between the level of injury and the closest region that can be measured for motor function!

In contrast, in the cervical study that we just announced, we will be evaluating the Neuro-Spinal Scaffold™ implant in patients with AIS A injuries at levels C5-T1. Every one of these levels has a measurable motor function that is included in the ISNCSCI exam. Specifically, the following muscles (with the corresponding innervating level) are bilaterally assessed in the ISNCSCI exam:

C5 – elbow flexors
C6 – wrist extensors
C7 – elbow extensors
C8 – finger flexors
T1 – small finger abductors
The C5-T1 region of the spinal cord is only about 2-2.5 inches long. If the Neuro-Spinal Scaffold were able to preserve, remyelinate, and/or regenerate just a small area of spinal cord, we believe this could have significant functional consequences.

As a specific example, if a patient with an AIS A injury at C7 were to experience two levels of neurological improvement to T1 (C7 and T1 are just over an inch apart), it could be the difference between having minimal-to-no hand function to having substantial-to-complete hand function. Improvements in this area have the potential to positively impact a person’s ability to interact with his or her environment. Daily activities such as feeding and bathing could be dramatically improved, which could lead to enhancements in overall quality of life.

Because of the importance of every inch and level of the cervical spinal cord, there is also increased risk of losing function in the event of any neurological worsening. However, the safety and ASIA Impairment Scale conversion data collected in the INSPIRE study are encouraging regarding the prospects of the Neuro-Spinal Scaffold in the cervical spinal cord. Our mission is to redefine the life of the SCI patient. With cervical spinal cord injuries accounting for a significant proportion of overall SCI, and representing the most severely-affected patients, we couldn’t be more enthusiastic about initiating this new study.

Mark Perrin
CEO & Chairman
March 23, 2017

How the 21st Century Cures Act Impacts InVivo - December 19, 2016

How the 21st Century Cures Act Impacts InVivo – December 19, 2016

The 21st Century Cures Act passed the House and the Senate, and President Obama signed it into law on December 13. The Act provides immediate benefits for both patients and companies developing therapies for patients with orphan diseases or conditions. InVivo Therapeutics is studying the Neuro-Spinal Scaffold™ in patients with complete paralysis (no motor or sensory function below the level of injury) as a result of an acute spinal cord injury. We are utilizing the Humanitarian Device Exemption (HDE) pathway through the FDA, which previously capped the eligible population of patients to be treated at 4,000 annually. At 4,000 patients per year, InVivo was confined to taking advantage of the HDE pathway only in patients with complete paralysis. Under the 21st Century Cures Act, that cap is lifted to 8,000 patients per year, which may allow InVivo to take advantage of the HDE pathway for many patients with incomplete (some motor or sensory function) paralysis as well. To better understand the immediate implications to our clinical development portfolio, it’s helpful to describe the key differences between the HDE pathway we’ve been following with the INSPIRE study and the Premarket Approval (PMA) pathway we previously would have had to follow to address incomplete SCI.

The FDA states that the “PMA is the most stringent type of device marketing application required by FDA.”1 To obtain approval through the PMA pathway, a sponsor has to demonstrate “safety and effectiveness” usually by conducting an appropriately powered pivotal study to demonstrate the investigational product is statistically superior to a control. This is a suitable way of evaluating investigational therapies if the disease has a large prevalence or incidence, because such trials usually involve hundreds of people. The challenges associated with running large trials with very small patient populations was one of the drivers behind the creation of the HDE pathway. The bar for approval set by the HDE pathway is “safety and probable benefit,” which allows for smaller trials and a more streamlined path to approval.

InVivo is currently exploring the best regulatory strategy for expanding our HUD population. If an expanded incomplete SCI population is approved, we would plan to study incomplete SCI patients in a new study (following the INSPIRE study) designed to support HDE approval.

Given the early compelling data from the INSPIRE pivotal study, the potential to address patients with incomplete paralysis via the HDE regulatory pathway is extremely appealing.  There are no approved therapies for spinal cord injury today, representing an enormous unmet medical need. InVivo is working every day to change that, and this legislation may allow for a more rapid path to expanding the clinical and commercial potential of the Neuro-Spinal Scaffold.

Mark Perrin, CEO & Chairman
December 19, 2016

References

  1. http://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/premarketsubmissions/premarketapprovalpma/

Safe Harbor Statement

Any statements contained in this CEO Perspective that do not describe historical facts may constitute forward-looking statements within the meaning of the federal securities laws. These statements can be identified by words such as “believe,” “anticipate,” “intend,” “estimate,” “will,” “may,” “should,” “expect,” “designed to,” “potentially,” and similar expressions, and include statements regarding the safety and effectiveness of the Neuro-Spinal Scaffold; the company’s ability to commercialize its products; the company’s ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the company’s products and technology in connection with the treatment of spinal cord injuries; the availability of substantial additional funding for the company to continue its operations and to conduct research and development, clinical studies and future product commercialization; and other risks associated with the company’s business, research, product development, regulatory approval, marketing and distribution plans and strategies identified and described in more detail in the company’s Annual Report on Form 10-K for the year ended December 31, 2015, and its other filings with the SEC, including the company’s Form 10-Qs and current reports on Form 8-K. The company does not undertake to update these forward-looking statements.

CEO's Perspective - October 19, 2016

CEO’s Perspective – October 19, 2016

Given recent events, I thought it was an appropriate time to update our stakeholders on the current status of our INSPIRE clinical study. We have made significant progress over the last year notwithstanding the impact of several external factors on our clinical development timelines. In this CEO Perspective, I will provide additional background on these factors and our updated projected timelines.

INSPIRE Study Update

As previously communicated, INSPIRE patient enrollment was put on hold in May as a result of the FDA’s pre-specified hold at 12 patients to review six-month safety data from the first five patients. The submission of the safety data package was made in April, and in May there was a marked increase in patient enrollment such that we hit the 12 patient ceiling.  We believed the FDA would allow us to continue to enroll patients after reviewing the favorable five patient six-month safety data; however, the FDA requested relatively minor changes to the protocol before allowing for the expansion of the INSPIRE study.

The changes to the protocol that the FDA requested did not involve changes to the inclusion or exclusion criteria for the study and they were not in any way related to the two patient deaths. As previously stated, the deaths were deemed by all parties to be unrelated to the Neuro-Spinal Scaffold™ and the implantation procedure. None of these protocol modifications should impact enrollment rates.

At the time of the FDA-approved protocol amendment for the expansion, we were hopeful that we would still be able to achieve our goal of approaching full enrollment by the end of the year and completing enrollment in the first quarter of 2017.  However, because all sites were required to resubmit the protocol amendment to their Institutional Review Boards (IRBs), we had no sites open in June, only five sites open by the end of July, and 13 sites by the end of August; we did not get up to 20 sites open until Sept 19.

Recently, we updated our corporate presentation to state that we are now projecting to complete enrollment in the INSPIRE study in the first half of 2017 rather than the first quarter. We are, of course, doing everything in our power, including having frequent interaction with study investigators and coordinators, to get enrollment completed as quickly as possible.

We have had 20+ sites open for only a few weeks, and we are optimistic that with this many sites open, enrollment will be quicker. In May, which was the last time we had 20 sites open, there were no enrollments for two weeks, but then two enrollments on one day, followed by another eligible patient who presented the very next day.

The neurosurgeons at our study sites are engaged and motivated to enroll subjects. In addition to the announced presentations at the recent Congress of Neurological Surgeons (CNS) meeting, we had an INSPIRE Steering Committee at CNS attended by 14 of the study neurosurgeons, including several of the most prominent researchers in the field.

Lastly, as we have previously disclosed in connection with the protocol amendment, the FDA reintroduced as a Study Design Consideration the concept of having a control group as part of our clinical development program.  We are continuing to address this issue with the FDA.

A year ago the INSPIRE study did not even exist. We had just enrolled our fifth patient into a pilot study. Over the last year, we have incorporated that pilot study into the pivotal probable benefit INSPIRE study, opened 10 new sites, and implanted five additional patients. We are on track to be able to fully enroll the study in the first half of 2017, and expect to complete the study in the second half of 2017 and submit for HDE approval in late 2017 or early 2018. The results to date in the INSPIRE study are encouraging, and we believe that the Neuro-Spinal Scaffold could be the first product ever approved for the treatment of acute spinal cord injury.

Cervical SCI Program Update

In the most recent corporate presentation, we also noted that the FDA did not approve our pilot study to evaluate the Neuro-Spinal Scaffold in cervical spinal cord injury. Disapprovals from the FDA on initiating a new clinical trial, particularly with regard to a high-risk/high-reward indication such as cervical SCI, are not uncommon.  We believe that the safety profile observed to date (no Serious Adverse Events related to the scaffold or implantation) supports moving into this severely affected patient population with a significant unmet medical need, and we have initiated conversations with the FDA on this topic. We are working diligently to address the remaining FDA deficiencies, and in parallel we are pursuing initiation of the trial outside of the U.S.  We anticipate being able to open the pilot study in Canada in the first half of 2017 and will look to expand the study to European countries.

Conclusion

Financially, we are in a strong position with cash that should last through 2017.  By that time, the INSPIRE study should be completed and we expect to have filed or be preparing to file for HDE approval. The unexpected shutdown in enrollment over the summer and the resulting adjustment in timelines is frustrating to everyone, but I want to underscore that the InVivo team continues to diligently and passionately drive the fundamentals of our business to achieve the goal of redefining the life of the spinal cord injured patient.  We look forward to communicating continued success and progress over the next year, which should be the most exciting in the history of the company.

Safe Harbor Statement

Any statements contained in this CEO Perspective that do not describe historical facts may constitute forward-looking statements within the meaning of the federal securities laws. These statements can be identified by words such as “believe,” “anticipate,” “intend,” “estimate,” “will,” “may,” “should,” “expect,” “designed to,” “potentially,” and similar expressions, and include statements regarding the safety and effectiveness of the Neuro-Spinal Scaffold; the company’s ability to commercialize its products; the company’s ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the company’s products and technology in connection with the treatment of spinal cord injuries; the availability of substantial additional funding for the company to continue its operations and to conduct research and development, clinical studies and future product commercialization; and other risks associated with the company’s business, research, product development, regulatory approval, marketing and distribution plans and strategies identified and described in more detail in the company’s Annual Report on Form 10-K for the year ended December 31, 2015, and its other filings with the SEC, including the company’s Form 10-Qs and current reports on Form 8-K. The company does not undertake to update these forward-looking statements.

Epidemiology and Market Opportunity Around the World - July 13, 2016

Epidemiology and Market Opportunity Around the World – July 13, 2016

We at InVivo are driven by our mission to redefine the life of the spinal cord injury (SCI) patient.  Although we have been focused to date on SCI patients in the United States, we realize that the tremendous burden of SCI does not end at our borders. We recognize that traumatic spinal cord injury is a global problem and today’s announcement to expand clinical operations into Canada is a significant step toward addressing that problem. Our goal is to be the worldwide leader in SCI and to one day treat patients around the world with a portfolio of products that have a significant impact on their lives.

Following is a brief overview of various reported incidence and prevalence rates as clarification of the impact of spinal cord injury around the world and the global problem we are working to address.

Defining Incidence and Prevalence

In the case of traumatic spinal cord injury, incidence refers to the number of new cases of spinal cord injuries that have occurred due to traumatic events — such as motor vehicle accidents and falls — over a year. Prevalence, on the other hand, refers to the proportion or number of a group of individuals    having a clinical condition at a given point in time. For traumatic spinal cord injury, the prevalent population is all of the people currently living in a wheelchair or experiencing deficits as a result of a spinal cord injury. Both numbers are often expressed as rates in terms of cases or individuals per million inhabitants per year. Multiplying the incidence and prevalence rates by the population of a country or region will yield a rough estimation for how many people in that country or region are newly injured in a given year and how many people are living with a spinal cord injury, respectively.

Limitations of Estimating SCI Rates

Epidemiology is the study of the causes, incidence/prevalence, distribution, and control of conditions. Although estimating incidence and prevalence may seem like it should be a simple counting task, the field of epidemiology is actually quite complicated. In large countries, there are rarely all-inclusive registries of patients with a given condition across the entire country. Instead, studies usually focus on a smaller region (like a city, state, or province) and often use imperfect identification methodology. For example, many epidemiology studies for spinal cord injury rely on the use of diagnosis codes (in the U.S. ICD-9/10-CM codes), but these codes can be used incorrectly, and it can be challenging to discern a true acute, traumatic SCI hospitalization from a follow-up or rehabilitation hospitalization.

Epidemiology in the United States and Canada

A recent review by Furlan et al [1] summarizes studies that have evaluated the incidence of acute traumatic SCI around the world. The Furlan article cites 14 different studies in the United States that evaluated different geographies (eg, Utah, San Diego, New York State) and utilized different identification methodologies (eg, registries, surveys, diagnosis codes). Most of the studies evaluated incidence rates in the 1980s or 1990s. Recent (since 1980) incidence rate estimates ranged from 23.9/million/year (Colorado) to 83/million/year (Alaska). The median incidence rate from the 14 studies was about 40/million/year, and this figure has been widely used in the spinal cord injury field.

Multiplying this rate by the U.S. population yields an incidence estimate of about 12,000-13,000 new injuries per year.

The National Spinal Cord Injury Statistical Center (NSCISC) traditionally has used the incidence rate estimate of 40/million/year, but in its most recent Facts and Figures publication, NSCISC started using an incidence rate of 54/million/year [2]. This incidence rate comes from a recent study conducted by Jain et al [3] in 2012, and yields an annual incidence of approximately 17,000 new cases per year. This is    notably higher than the previous estimate. For now, we at InVivo will continue to use the   40/million/year number in our market size estimates, but we are constantly evaluating the literature for updates and additional information. We may adopt the higher estimate in the future.

In Canada, the incidence rates are about the same as in the US. In a widely-cited recent study, Noonan   et al [4] estimated the discharge incidence of traumatic SCI to be 41/million/year. Since the Canadian population is almost an order of magnitude smaller than the United States, this incidence rate translates to just under 1,500 new cases per year in the country.

As there are no available treatments to effectively change the course of this condition, the vast majority of the incident population moves into the prevalent population. DeVivo et al [5] estimates the prevalent population to be 906 per million persons in the United States and Noonan et al [4] estimates 1,288 per million persons in Canada. This translates to roughly 290,000 and 44,000 prevalent cases in the United States and Canada, respectively.

Epidemiology in Europe and Japan

Incidence and prevalence estimates across Europe vary significantly. According to Furlan et al [1], incidence rates were reported as low as 8/million/year in Spain and as high as 131/million/year in Bulgaria. For studies performed in European Union (EU) member countries, the median incidence rate was 19.4/million/year. Using this incidence rate, the incidence of SCI in EU countries is estimated to be about 10,000 per year. Prevalence rates ranged from 227 to 419 per million persons in Sweden and Norway, respectively. Although reported incidence and prevalence rates in Europe are lower than those in the United States and Canada, there is still a large market opportunity in Europe. We look forward to announcing our first INSPIRE site in Europe in the coming months as a first step on the path to European commercialization.

Japan represents another significant market for our products. The median reported incidence rates from Furlan et al [1] is 39.4/million/year, which yields an annual incidence of about 5,000 new SCIs per year. Although we do not have any immediate plans for initiating clinical studies in Japan, we have already engaged in preliminary discussions with potential Japanese partners.

SCI: A Worldwide Problem

My hope in describing these epidemiology rates is twofold: first, to demonstrate that spinal cord injury is a global problem that affects populations across the world; second, to demonstrate that SCI epidemiological data are imperfect and that incidence and prevalence estimates can vary widely from source to source and study to study. Many of the cited authors stressed the need for a more formal and rigorous spinal cord injury recording and reporting system. Until countries formalize a system to effectively capture spinal cord injury data, it will be impossible to know exactly how many individuals suffer from acute and chronic SCI.

At InVivo, our mission stands without prejudice to country of origin, and while our clinical strategy to date has been U.S.-centric, over the next several years we plan to execute on a clinical, regulatory, commercialization, and business development strategy that will allow us to address SCI patients across the globe.

Mark Perrin, CEO and Chairman
July 13, 2016

References

  1. Furlan, Julio , et al. “Global incidence and prevalence of traumatic spinal cord injury.” The Canadian Journal of Neurological Sciences 40.04 (2013): 456-464.
  2. National Spinal Cord Injury Statistical Center, Facts and Figures at a Birmingham, AL: University of Alabama at Birmingham, 2016.
  3. Jain, Nitin , et al. “Traumatic spinal cord injury in the United States, 1993-2012.” JAMA 313.22 (2015): 2236-2243.
  4. Noonan, Vanessa , et al. “Incidence and prevalence of spinal cord injury in Canada: a national perspective.” Neuroepidemiology 38.4 (2012): 219-226.
  5. DeVivo, Michael , et al. “Prevalence of spinal cord injury: a reestimation employing life table techniques.” Archives of neurology 37.11 (1980): 707-708.
The INSPIRE Study - February 29, 2016

The INSPIRE Study – February 29, 2016

Today we announced the Objective Performance Criterion (OPC) for The INSPIRE Study. The OPC is a significant design element of this study, and now that it has been established in the latest FDA-approved protocol amendment, I thought it would be a good time to reflect back on the history of this study, which is intended to serve as the basis of approval for our first product.

Humanitarian Use Designation

The story of The INSPIRE study begins with the granting of Humanitarian Use Device (HUD) designation to the Neuro-Spinal Scaffold™ in April 2013. HUD designation is similar in some ways to the “orphan” status that is granted to drugs and biologics in that they both apply to small patient populations. In the case of an HUD, a sponsor has to show that the HUD population is fewer than 4,000 patients per year in the United States. Our HUD population is made up of patients with acute, traumatic, complete (AIS A) thoracic and cervical spinal cord injury (SCI), excluding patients with lacerating injuries (e.g., gunshot and knife wounds). The FDA grants this designation to spur development of devices to treat patients for whom there are no other comparable options.  For patients with acute complete traumatic spinal cord injury, there is no treatment that changes the natural course of recovery.  For the large majority of these patients, recovery is negligible or absent.

Probable Benefit

Because of the significant unmet medical need in patients who are completely paralyzed (no movement and sensation below the injury nor bowel and bladder control), our HUD designation allows us to apply for Humanitarian Device Exemption (HDE) approval, which has a lower threshold to approval than traditional approval pathways. An HDE needs to demonstrate safety and that the probable benefit to a patient’s health from the use of the device outweighs the risk. This threshold for approval has allowed us to design The INSPIRE Study as a small, efficient study using historical benchmarks to assess probable benefit. This faster and easier pathway to approval enables earlier access to innovative, disease-modifying new devices.

The Pilot Study

The INSPIRE Study began as a five-patient pilot study with an initial focus on the safety and feasibility of the Neuro-Spinal Scaffold  and the associated novel implantation procedure. Entering the spinal cord to implant a device following acute traumatic SCI is a revolutionary new idea.  Doing so follows a similar paradigm used to treat acute traumatic brain injuries, but required testing to demonstrate safety and feasibility in the early hours and days following injury. The pilot study originally incorporated an enrollment hold for each of the five patients to review three months of safety data.

The study was initiated in April 2014, and the first patient was enrolled in October 2014. In December 2014, we announced that the durations of the holds between the first three patients had been reduced and that patients three through five could be enrolled in parallel. This was made possible by the demonstration of a straightforward surgical procedure and, most importantly, by the lack of any serious adverse events associated with either the implantation or the Neuro-Spinal Scaffold.  The safety and feasibility profile of the Neuro-Spinal Scaffold and our collaborative relationship with the FDA enabled a substantial shortening of the clinical trial timeline.

The INSPIRE Study

As recently as November 2014, we envisioned a standalone, randomized, controlled pivotal trial consisting of 50-100 patients. However, as we reviewed the encouraging initial results from our pilot study, we started to contemplate taking a more streamlined approach. In the summer of 2015, we first proposed to the FDA the idea of expanding the pilot study into a pivotal study and using historical benchmarks to define an OPC. Following several productive discussions and submissions, in December 2015 we unveiled our plan for The INSPIRE Study, which included the conversion of our pilot study into a 20-patient pivotal probable benefit study, inclusive of the 5 patients in our pilot trial.

In addition to the conversion of the study and the establishment of the primary endpoint and study size, there were several other advantageous study modifications. The minimum age for enrollment was lowered from 18 to 16 and the highest level of injury was raised to T2. There is a sharp increase in the incidence of traumatic SCI in adolescents older than 15, most likely associated with a typical legal driving age of 16 years.  Spinal cord injured-patients aged 16-18 represent a group we are keenly interested in helping.  We estimate that these two changes together increased the eligible patient population by about 11%, which should help to increase enrollment rates. 1

Announcing The INSPIRE Study was a remarkable accomplishment for our team and company, but there were still ongoing discussions regarding the OPC.  An OPC is a measure of study success that is used in clinical studies designed to demonstrate probable benefit in support of an HDE approval. Today we announced that the OPC for The INSPIRE Study is defined as 25% or more of the patients in the study demonstrating an improvement of at least one ASIA Impairment Scale (AIS) grade at six months post-implantation. Large, multinational, natural history databases consistently indicate that only 12-16% of patients with complete (AIS A) thoracic injury will convert to an improved AIS grade following standard care within six months after injury. Although our OPC is the fundamental component to demonstrate probable benefit, it is important to note that the OPC is not the only variable that the FDA evaluates when reviewing an HDE application. Approval is not guaranteed if the OPC is met, and even if the OPC is not met, the FDA may approve a therapy if probable benefit is supported by a comprehensive review of all clinical endpoints and preclinical results, as demonstrated by the sponsor’s body of evidence. The INSPIRE Study includes a number of secondary endpoints that are meaningful to patients, including bowel and bladder function, depression, quality of life, and pain (which is often severe and debilitating).

This study has demanded innovative thinking and dedicated hard work from the InVivo management team and scientists, in close collaboration with influential thought leaders in the field of neurosurgery. The FDA has been a supportive partner throughout this process during the review and approval of ten protocol amendments that have allowed us to arrive at this point.

The INSPIRE Study is proposing and testing a medically compelling new approach to the treatment of spinal cord injury that has the potential to completely change the standard of care for these devastating injuries. Initially, neurosurgeons were reasonably cautious about such a bold, innovative approach but are now showing great interest and increasing confidence in the potential of the Neuro-Spinal Scaffold. Due to the excellent safety profile of the Neuro-Spinal Scaffold implant and the encouraging pilot study results to date, we are now poised to execute on our goal of approaching full enrollment of the pivotal probable benefit study by the end of the year, which will allow for an HDE submission in 2017.

I want to thank the employees of InVivo, our investigators, and their patients for their extraordinary contributions. This will be an exciting year for InVivo, and I look forward to communicating our progress.

Mark Perrin, CEO and Chairman
February 29, 2016

1National Spinal Cord Injury Statistical Center, University of Alabama at Birmingham, 2014 Annual Statistical Report – Complete Public Version

InVivo in 2016: Looking Ahead - December 17, 2015

InVivo in 2016: Looking Ahead – December 17, 2015

This year was one of tremendous progress for InVivo. In 2015, we uplisted to a major stock exchange, completed enrollment of the pilot stage of the pivotal probable benefit INSPIRE study, communicated encouraging early clinical data, and engineered an accelerated regulatory plan to bring the Neuro-Spinal Scaffold that much closer to commercialization. However, as we are on a mission “to redefine the life of the spinal cord injury (SCI) patient” – and realizing the ultimate goal is still in front of us – I’d like to outline what lies ahead for 2016 and how we plan to continue to create fundamental value for our most important partners: shareholders and patients.

Propelling through the INSPIRE study

We have continued to foster a collaborative and fruitful relationship with the Food and Drug Administration (FDA) that has allowed us to dramatically shorten traditional clinical development timelines. In December 2015, we unveiled our plan for the INSPIRE study, including the conversion of our pilot study into a pivotal probable benefit study. Having laid the critical groundwork for INSPIRE, in 2016 we will set out to:

  • Announce an Objective Performance Criterion (OPC) for INSPIRE
  • Expand the INSPIRE study to the full 20 patients
  • Announce at least 10 new INSPIRE sites, with 7 coming on board in the first half of the year
  • Approach full enrollment of INSPIRE by the end of the year
  • Announce results from the INSPIRE study as appropriate

Obtaining marketing approval for the Neuro-Spinal Scaffold is inherently different from obtaining marketing approval for many devices because of the accelerated regulatory pathway we have chosen – Humanitarian Device Exemption (HDE). Unlike a Premarket Approval (PMA), for which a sponsor usually has to power and conduct a pivotal study that demonstrates the investigational product is statistically superior to a control, an HDE only requires the demonstration of safety and probable benefit, which is a lower regulatory hurdle. In order to assess probable benefit, HDE sponsors can establish an Objective Performance Criterion (OPC) to prospectively define success in an uncontrolled study. We are in late-stage discussions with the FDA regarding the definition of the OPC, using historical benchmarks from large, well-established natural history databases as a guide. Once the OPC is agreed upon, we should have a clear view of the likely path to commercialization. Of course, the OPC is not the only variable that the FDA evaluates when reviewing an HDE application. Approval is not guaranteed if the OPC is met, and even if the OPC is not met, the FDA may approve a therapy if safety and probable benefit is supported by a comprehensive review of all clinical endpoints and preclinical results.

In parallel to the OPC discussions with FDA, we will continue to enroll patients, and we expect the FDA will authorize us to expand the number of patients to the full 20 in 2016. We hope to be approaching full enrollment by the end of the year, which will hinge upon a steady ramp-up of clinical sites. We are targeting as many as 10 new sites by year-end, with 7 coming on board in the first half of the year. In addition to several more sites in the U.S., we plan to open our first ex-U.S. sites in Canada and the United Kingdom.

It is extraordinary to think that just over a year after enrolling the first patient in our study, we are now running a pivotal trial with planned international expansion and the potential to file an application for HDE approval in just two years.

Value Beyond INSPIRE – Cervical SCI and Bioengineered Neural Trails™

In addition to all of the exciting progress with the INSPIRE study in which we are investigating the Neuro-Spinal Scaffold in patients with acute, neurologically complete thoracic SCI, we also expect to make significant progress in 2016 with our programs dedicated to cervical and chronic SCI. To that end, we recently announced our plans to initiate in mid-2016 a study for acute, neurologically complete cervical SCI. The importance of moving higher in the spinal cord cannot be overemphasized, as cervical SCI represents a higher-risk/higher-reward condition than thoracic SCI. In general, gaining or losing a single neurological level in patients with thoracic injuries may have minimal impact on the patient’s overall function and quality of life. However, in the cervical cord, a single level often makes a dramatic difference. We are highly encouraged by the safety profile of the Neuro-Spinal Scaffold in the INSPIRE study to date, and we look forward to testing the Neuro-Spinal Scaffold in injuries where small changes in neuronal preservation or regrowth may have substantial impact on function. I’ll devote an entire CEO’s Perspective on the importance of pursuing a treatment for cervical SCI when we officially launch the program (mid-2016).

We are also devoting significant resources to advancing our Bioengineered Neural Trails program for the 276,000 patients in the U.S. currently living with chronic SCI. Recently, we announced the acquisition and filing of foundational intellectual property for this exciting new approach to stem cell therapy for chronic SCI. We’ll continue to update the public with our progress in this area and are targeting a pre-IND (Investigational New Drug) meeting with the FDA by the end of 2016, which will help inform our development and clinical plans for the program.

This has been a fantastic year of progress for InVivo, but I believe that 2016 will be even more exciting as we continue to move closer to our goal of redefining the life of the spinal cord injury patient.

Mark Perrin, CEO and Chairman
December 17, 2015

Building Value in a Pre-commercialization Biotech Company: Importance of Increased Exposure Within the Scientific and Medical Communities - September 21, 2015

Building Value in a Pre-commercialization Biotech Company: Importance of Increased Exposure Within the Scientific and Medical Communities – September 21, 2015

A company in a pre-launch phase has the ability to create foundational value by educating stakeholders within the scientific and medical community about their novel therapeutic approach. At InVivo, we believe surgical implantation of the Neuro-Spinal Scaffold™ device has the potential to establish a beneficial paradigm shift in the treatment of acute spinal cord injury (SCI). However, it is our responsibility to increase awareness of our approach within the clinical community. Rooted with strong scientific evidence and rationale, InVivo intends to extend its reach into scientific and medical communities through increased non-promotional participation at leading neurosurgical and rehabilitation meetings as well as through publishing pre-clinical and clinical findings in reputable journals. Increased presence at medical meetings allows us the opportunity to develop relationships with prominent decision-making societies, such as the Congress of Neurological Surgeons (CNS) and American Association of Neurological Surgeons (AANS), and interface with key opinion leaders in the field. Publishing new findings in peer-reviewed journals confirms the scientific rigor with which the results were obtained and further validates our clinical approach.

Medical Education Begins Pre-launch Through Increased Participation at Scientific and Medical Meetings

The process to increase scientific exposure and educate the medical community has already begun at InVivo, with significant accomplishments made over the past 12 months. During this time we have presented and exhibited at the following meetings:

October 2014: Tom Ulich, M.D., Chief Scientific Officer, presented at the annual Stem Cell Meeting on the Mesa. Dr. Ulich discussed InVivo’s approach to both acute SCI and chronic SCI through the combined use of scaffolds and neural stem cells. [link to video presentation]

October 2014: InVivo exhibited at the annual Congress of Neurological Surgeons (CNS) meeting in Boston, MA. InVivo took the opportunity at this meeting for site recruitment and to discuss our pilot trial with potential Principal Investigators (PIs).

March 2015: InVivo exhibited at the Southern Neurosurgical Society (SNS) annual meeting in Naples, FL. Domagoj Coric, M.D., president of the society and the neurosurgeon who implanted Subjects #2 and #3, narrated the intraoperative video to educate fellow surgeons about our novel technique.

May 2015: InVivo exhibited at the American Association of Neurological Surgeons (AANS) annual meeting in Washington, DC. In addition, James Guest, M.D., Ph.D., presented preclinical findings from a porcine SCI model conducted in collaboration with InVivo. Furthermore, Alexander Ropper, M.D., presented an
e-Poster highlighting the surgical technique and three-month clinical findings of Subject #1. [links to Dr. Guest and Dr. Ropper abstract PDFs]

June 2015: InVivo Co-Founder, Dr. Robert Langer, highlighted the company’s scientific progress in his closing keynote address at the International Society for Stem Cell Research in Stockholm, Sweden.

June 2015: Richard Layer, Ph.D., Director of Research, presented a poster highlighting our pre-clinical findings in a rat contusion model at the Annual Symposium of the National Neurotrauma Society in Santa Fe, NM. [link to e-poster PDF]

September 2015: Alex Aimetti, Ph.D., Sr. Director, Medical Education and Scientific Support, presented a poster highlighting the clinical translation of the Neuro-Spinal Scaffold including pre-clinical and clinical data at the Annual Spinal Research Network Meeting in London, UK. Prominent external authors of the abstract include James Guest, M.D., Ph.D. (Scientific Advisory Board member), Nicholas Theodore, M.D. (PI, neurosurgeon who implanted Subject #1), and Domagoj Coric, M.D. (PI, neurosurgeon who implanted Subjects #2 & #3). [link to e-poster PDF]

September 2015: Alex Aimetti, Ph.D., Sr. Director, Medical Education and Scientific Support, presented a poster at the Tissue Engineering and Regenerative Medicine International Society’s World Congress in Boston, MA, highlighting the Neuro-Spinal Scaffold mechanism of action. Dr. Aimetti also participated in a panel discussion regarding translating promising academic discoveries to future commercial products. Robert Langer, ScD, highlighted InVivo’s work in his opening keynote address at the meeting.
[link to e-poster PDF]

This initiative will only continue to grow as we head toward commercialization. Future meetings we plan to target are:

September 2015: Congress of Neurological Surgeons annual meeting in New Orleans, LA

October 2015: Stem Cell Meeting on the Mesa in La Jolla, CA March 2016: AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves Annual Meeting in Orlando, FL. InVivo will be hosting our first major symposium at a medical conference.

April 2016: American Association of Neurological Surgeons (AANS) annual meeting in Chicago, IL

Publishing Key Pre-clinical and Clinical Findings in Reputable Journals Validates Our Novel Therapeutic Approach

Submitting data for peer-reviewed evaluation is another method to build credibility within the SCI scientific and medical circles. Independent experts in the field evaluate the manuscript and recommend publication based on the methodology of the study and the impact of the results. InVivo is currently aiming to publish three manuscripts in the near future. One manuscript highlights the company’s landmark studies using a hemisection model in non-human primates. Another manuscript focuses on the surgical feasibility of Neuro-Spinal Scaffold implantation in a porcine contusion model. The third planned manuscript discusses the first human case and includes clinical findings up to six months. These publications will add to the scientific rationale regarding our therapeutic approach as we attempt to change the way in which spinal cord injury is treated.

InVivo’s Commitment to Medical Education

Spinal cord injury remains a therapeutic area with a huge unmet need. As leaders in the field, InVivo remains committed to bringing innovative products to market that improve the lives of these individuals. We are not developing the next ”me-too” therapies. We are pioneering a transformative therapeutic approach that, up until recently, has never been studied in humans. To drive awareness and ― ultimately ― adoption of this procedure, it is our job to educate key members within the scientific and medical communities. We will continue to ramp up efforts to increase exposure at medical meetings and publish our collaborative work with experts in the field. This company was founded on strong science, and it remains in our DNA to provide data-driven evidence of the beneficial effects of our multimodal therapeutic approaches to treat spinal cord injury.

Corporate Financing - What are the options? - July 29, 2015

Corporate Financing – What are the options? – July 29, 2015

The vast majority of development-stage public companies will need to tap into the capital markets at several points in their development cycle to fund critical investments that will ultimately benefit all of a company’s stakeholders – shareholders included. Public companies have a number of options at their disposal by which they can access these markets. This article will touch upon the major corporate financing options at a high-level and will provide an explanation as to why InVivo has decided to enter into an At-the-Market (ATM) equity offering sales agreement with Cowen and Company, LLC.

Confidentially Marketed Public Offerings (CMPOs)

Sometimes referred to as “pre-marketed” or “overnight” offerings, CMPOs are utilized by many public companies to access capital markets due to their rapid execution times and short periods of public exposure. In terms of mechanics, the public company (or “issuer”) engages a broker-dealer to act as an underwriter on a firm-commitment basis, which means that the underwriter directly purchases the securities from the issuer, guaranteeing the size of the offering, and then resells them to investors. To start the process, the underwriter approaches several potential institutional investors without identifying the issuer they are representing and asks if they want to receive confidential information about the issuer’s offering. If the potential investor agrees, the issuer’s identity is revealed and negotiations regarding specific parameters (size, discount, structure, etc.) begin. At this stage, there is no public announcement signaling an imminent offering to the market. Once the issuer and institutional investors agree to basic terms, the deal flips from a confidential offering into a public offering shortly before pricing, and a retail component is added to the offering. The offering finally gets priced and executed on an overnight basis with the specifics being announced before market open of the subsequent trading day. InVivo’s raise in May 2014 was a CMPO.

Registered Direct Offerings (RDOs)

This financing vehicle is very similar to a CMPO with regard to speed and efficiency, but the key differences are that there is no retail component (i.e., the entire offering is purchased by a few institutional investors) and the broker-dealer serves as a placement agent using “best efforts” to place a specified amount of securities with institutional investors.  That is, the placement agent does not provide a firm commitment to purchase the securities directly, and there is no guarantee that any specified amount of securities will be sold. Similar to a CMPO, an RDO is marketed confidentially and without any prior public market announcement of the offering until pricing. InVivo’s raise in January 2015 was an RDO.

Traditional Follow-On Offering

These types of traditional corporate financing vehicles are typically pursued by seasoned issuers, since the public marketing process provides more exposure to broader market trading during the offering marketing process. In a traditional follow-on offering, an announcement about a potential offering is made to the markets via SEC filings and a press release typically a number of days before the pricing of the offering (much longer if the company does not have an effective shelf registration statement). Since the market has advance notice, market participants may short or sell the stock in the period between the offering announcement and pricing, which could lead to a more dilutive event (the company will have to issue more shares to hit its intended deal size).

At-the-Market (ATM) Financing

ATMs provide issuers the ability to sell publicly tradable shares at the prevailing market price without the pre-determined pricing or volume parameters, large discounts, warrant coverage, greater dilution, and other higher costs of capital typically associated with the other described deal structures. This offering type allows issuers to direct the timing and size of transactions and to create a controlled flow of shares into the market at prices the issuer deems attractive, without sacrificing price stability and without the need for extensive pre-deal marketing or special selling efforts. In an ATM, the issuer’s shares are sold through a designated broker-dealer, acting as a sales agent, at prevailing market prices to natural interest in an existing secondary market. Although the issuer has complete control of when to turn the ATM program on and off, most ATM firms provide an algorithmic trading service to execute the transactions designed to mitigate stock price volatility by timing market executions to take advantage of optimal stock prices, resulting in less dilution. Sales are typically executed anonymously, thereby ensuring that the market will not be aware of when or if sales are being made through the ATM facility, with the results of sales disclosed at the end of each fiscal quarter, greatly limiting arbitrage or speculation concerning the size or pricing of specific sales. ATM facilities can be implemented quickly and efficiently relative to other types of financing, usually within a few weeks and, once in place, the issuer can access cash quickly, as-and-when needed, in an orderly, flexible fashion and can more precisely match the timing of sales of securities with the issuer’s need for cash, so that capital is deployed efficiently.

On July 29, we established an ATM with Cowen and Company, in part due to their broad range of financing vehicles and services. Cowen and Company is a world-leading provider of customized trading algorithms and ATM services. In addition, they offer comprehensive investment banking services, including equity, equity-linked and debt financings and mergers and acquisitions advisory services.

We view Cowen as a well-respected, long-term partner, and feel that the Cowen ATM provides us with a quick, flexible, and cost-effective means of raising equity capital in amounts and at times of our choosing, at prices we deem most attractive.

We reiterate our commitment to complete transparency on all fronts, and look forward to using the proceeds from this equity offering program to further advance the company’s mission: to redefine the life of the spinal cord injury patient.

Mark Perrin, CEO and Chairman
July 29, 2015

Social Media: The New Frontier - June 3, 2015

Social Media: The New Frontier – June 3, 2015

Ten years ago, while the concept of social networking certainly existed, the phrase “social media” was not on the tip of everyone’s daily tongue. Then came Facebook, launched publicly in 2006, and the world changed.

A few quick statistics: to date, Instagram has 75 million daily users; LinkedIn has 347 million members; Twitter has 236 million monthly users; and the behemoth, Facebook, had 1.44 billion active users as of first quarter 2015.

Clearly, social networking is here to stay.

So what does this information juggernaut mean to clinical trials in the pharmaceutical and medical device industry? When we consider the above-mentioned sites in addition to Google+ and Pinterest and Tumblr and Snapchat and Vine and so on, this cultural phenomenon, technology aside, is simply about people talking to each other. It’s about human interaction in a virtual setting. It’s about creating a digital identity on multiple platforms, including fourth screen technology. At the end of the day, it’s about social intelligence: we know who you are, we know where you are, we know what you look like, we know what you’re doing, and – where clinical trials are concerned – we know how you’re feeling.

The basic principles of clinical trials have not changed in spite of our new and vast and ever-growing social intelligence. Investigational drug and device protocols must still be approved by a regulatory body such as the FDA and adhered to. Reporting hasn’t changed, to the regulatory bodies, to the investors, and to the public. What has changed, however, is the way we look at our patients because now, thanks to social intelligence, we see them in a way we never did before. And we’re not the only ones looking. The investors are looking. The public is looking. The media is looking. Indeed, even the FDA is looking. While cliché to say, this is the truth: we have entered a brave new world.

As InVivo goes forward with its pilot trial and, down the road, with future studies, we are keenly aware that times have changed. There are the negatives of this all-eyes-on-study-subjects reality: patients “blind breaking” a trial, for example, by talking to each other, which has always happened but certainly never before on this level; violating patient privacy and confidentiality; disseminating inaccurate information; and jeopardizing the very integrity of the research. But as with any cultural evolution, there are also the positives: input from social media can provide real-time feedback from the patient’s individual perspective, and can enhance protocol design and program planning, ultimately in the interest of future patients.

Understanding how technology has changed the execution of clinical trials is an evolutionary process. There will be roadblocks. There will also be breakthroughs. InVivo, as a leader in spinal cord injury research and treatment, looks forward to helping pave the way to an appreciation of the evolving social intelligence landscape, and to clarifying how this massive communication shift can be leveraged to benefit all involved in the pharmaceutical and medical device industry.

Mark Perrin, CEO and Chairman
June 3, 2015

What NASDAQ has to Offer - April 16, 2015

What NASDAQ has to Offer – April 16, 2015

I am proud to report that our common stock will be listed on The NASDAQ Capital Market at the opening of trading on April 17, 2015. We expect that being listed on this national exchange will bring many benefits, from allowing for investments from a broader set of investors to increased exposure and trading oversight.

Immediately Appreciable Tangible Benefits

The most immediate benefit of our listing on NASDAQ is the removal of investment restrictions for larger investors. Many institutional investors have policies that prevent them from investing in OTC securities. We now have the opportunity to approach these institutional investors who were previously restricted from investing in us simply because of our OTC listing status. The benefits of uplisting also extend to our retail investors. Many brokers are required to have their clients sign a waiver stating they understand the risks associated with investing in OTC stocks, in addition to the waivers covering investing in general. Eliminating these additional requirements would allow more retail investors to analyze and invest in our company with the added confidence that NVIV is traded on the largest U.S. securities exchange.

A NASDAQ listing also comes with the benefit of additional trading oversight, which helps both the company and its investing stakeholders. NASDAQ MarketWatch actively monitors real-time data from broker/dealers for trading violations, i.e. manipulation. In the event NASDAQ’s MarketWatch Department notices unusual trading activity for NVIV, they will reach out to the company and its market makers in order to ascertain the cause of the unusual market activity. NASDAQ’s MarketWatch also oversees the complete and timely disclosure of material information by listed companies. This coordinated effort helps the company understand what is happening at the street level and ultimately, becomes beneficial to current and potential investors.

Long-term Benefits

Being listed on The NASDAQ Capital Market also puts us in a better position to be included in indices that are tracked by buy-side institutions. These include various NASDAQ and S&P indices as well as Russell 2000 & 3000. While there is no assurance that we will be included in any of these indices, becoming a NASDAQ-listed company accomplishes the very important first step. Further, there is an increased likelihood of analyst coverage, since many institutions are restricted from dealing with OTC-listed companies.

In short, by listing on NASDAQ, we join the ranks of the world’s most respected companies.

Mark Perrin, CEO and Chairman
April 16, 2015
Quick Facts

  • In 2014, the average three month average daily volume for an OTC-listed security increased almost 3X once upgraded to NASDAQ
  • NASDAQ listings include 3,500 companies and $9.1 trillion in market cap
  • 90% of the Fortune 500 companies are NASDAQ-listed
  • 4 out of the top 5 Fortune’s Most Admired Companies for 2015 are listed on NASDAQ
Reverse Splits and Uplisting - March 24, 2015

Reverse Splits and Uplisting – March 24, 2015

We view uplisting to NASDAQ — one of our corporate goals for 2015 — as an important and positive step in InVivo’s long-term growth strategy. One of the quantitative requirements for initial listing is that the closing price of our stock must be above $3.00 for 5 days. Properly executing our planned reverse stock split allows us to fulfill this crucial price requirement and reap the benefits of being on NASDAQ.

Ultimately, we believe the uplisting and higher stock price resulting from the reverse stock split will make our stock more attractive to a broader investor base. Currently, many institutional investors cannot invest in our company for a number of restrictive reasons, including our lower stock price, our trading on an OTC market, and related volatility. Furthermore, we will be in a better position to attract Wall Street analysts to cover our company’s progress with a higher stock price. The inherent increase in visibility associated with analyst coverage can also translate to greater liquidity for our shareholders.

Companies execute a reverse stock split for one of two primary reasons. It is important to discuss the distinction and motivation behind the two routes to fully appreciate what drives market perception of this action.

Reverse Stock Split by Companies to Avoid Delisting

Companies already listed on a major national exchange (NASDAQ or NYSE) must abide by a strict set of rules in order to maintain a listing. One such rule is a minimum price requirement; companies that have fallen under the threshold risk losing their listed status. These companies tend to be viewed as underperforming (as evidenced by their low stock price) and execute a reverse stock split simply to maintain their listing. In this case, the split is used to avoid the negative market perception of losing their listing.

Over 50% of reverse stock splits executed between 2010 and 2013 were in response to stock exchange deficiency notices, so it is no surprise that there is generally a negative market perception of a reverse stock split for this purpose.

Reverse Stock Split by Growing Companies to Gain a Listing

In comparison to companies executing a reverse stock split to maintain a listing, companies that execute a reverse stock split in order to uplist often have an upward trajectory. Such companies can often deliver positive stock price performance post-split as they take an important step in their growth. Other key attributes of companies that conduct successful splits and uplistings include having sufficient cash to reach near-term milestones, consistent news flow, and a commitment to transparency in communicating company goals with investors. InVivo intends to follow this trajectory.

In selecting the 1-for-4 reverse stock split ratio, we decided on a target price above
$10, which is an important psychological threshold for stocks. We evaluated previously executed reverse splits associated with an uplisting and found that 1-for-4 reverse splits priced in the $10 range generally performed well post-split.

We look forward to reporting to you on our anticipated success following our reverse stock split and planned uplisting and thank you for your ongoing support and confidence.

Mark Perrin, CEO and Chairman
March 24, 2015

This blog may contain forward-looking statements within the meaning of federal securities laws. Forward-looking statements can be identified by words such as “anticipates,” “believes,” “plans,” “will,” “intends,” “expects,” and similar references to the future, and include statements InVivo may make regarding its product development strategy, business prospects, and operational milestones. Readers should not unduly rely on these forward-looking statements, which are not a guarantee of future performance and are subject to a number of risks and uncertainties, many of which are outside InVivo’s control, which could cause its actual business and operating results to differ. For more information on the many factors that can result in actual performance differing from these forward-looking statements, please see the risk factors detailed in InVivo’s SEC filings. InVivo does not undertake to update these forward-looking statements.