SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

_____________________________

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the

Securities Exchange Act of 1934

 

Date of report (Date of earliest event reported): February 24, 2020 (February 20, 2020)

_____________________________

 

Seneca Biopharma, Inc.

(Exact name of registrant as specified in Charter)

 

Delaware   001-33672   52-2007292

(State or other jurisdiction of

incorporation or organization)

  (Commission File No.)   (IRS Employee Identification No.)

 

20271 Goldenrod Lane, 2 nd Floor, Germantown, Maryland 20876

(Address of Principal Executive Offices)

 

(301) 366-4960

(Issuer Telephone number)

 

 

  

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
   
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
   
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
   
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2). Emerging growth company ☐

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

 

Securities registered pursuant to Section 12(b) of the Act:

 

Title of Class   Trading Symbol   Name of Each Exchange on Which Registered
Common stock, par value $0.01 per share   SNCA   NASDAQ Capital Market

 

 

 

Item 7.01Regulation FD Disclosure.

 

On February 20, 2020, Seneca Biopharma, Inc. (“Company”) commenced an outreach process focused on out licensing its stem cell asset, NSI-566. Filed herewith as Exhibit 99.01 through 99.02 are the materials being used in such outreach.

 

The information contained in this Current Report on Form 8-K and the exhibits attached hereto shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall such information or such exhibits be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing. The information set forth in or exhibits to this Form 8-K shall not be deemed an admission as to the materiality of any information in this report that is required to be disclosed solely to satisfy the requirements of Regulation FD.

 

Item 9.01Financial Statement and Exhibits.

 

Exhibit No.   Description
99.01   Seneca Partnering Brief
99.02   Seneca Partnering Presentation

 

 

SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this Report on Form 8-K to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

Date: February 24, 2020 Seneca Biopharma, Inc.  
       
       
    /s/ Kenneth Carter  
    By: Kenneth Carter  
    Executive Chairman  
       

 

 

 

 

 

 

INDEX OF EXHIBITS

 

Exhibit No.   Description
99.01   Seneca Partnering Brief
99.02   Seneca Partnering Presentation

 

Exhibit 99.01

 

NSI - 566 STEM CELL PROGRAMS: PARTNERING BRIEF

 

 

SUMMARY OF OPPORTUNITY : PROGRAMS AND INDICATIONS NSI - 566 is an allogeneic neural stem cell line that is currently being evaluated in China in a placebo - controlled Phase II clinical trial for chronic ischemic stroke, and has been evaluated in the US in a Phase II trial for amyotrophic lateral sclerosis (ALS) and a Phase I trial for chronic spinal cord injury (cSCI) . NSI - 566 has been granted orphan drug designation by the US FDA for treatment of ALS . Seneca Biopharma, Inc . owns all rights to NSI - 566 and is seeking an asset sale, out - license, or global development partnership to further NSI - 566 development . Seneca Biopharma, Inc . , (NASDAQ : SNCA) is a clinical - stage biopharmaceutical company developing novel treatments for diseases of unmet medical need . NSI - 566 is the lead asset in Seneca’s pipeline and was developed using the Company’s proprietary neural stem cell technology . Seneca has generated a large patent estate in support of this technology, including approximately 50 issued and pending US and foreign patents with protection through 2023 to 2035 . The therapeutic basis and clinical benefits of NSI - 566 have been documented in over 30 peer - reviewed publications . NSI - 566 PIPELINE OVERVIEW : ALLOGENEIC, OFF - THE - SHELF THERAPY IN THREE INDICATIONS NSI - 566 is an allogeneic off - the - shelf neural stem cell line that has been evaluated in three clinical indications, each of which represents a substantial unmet medical need . MULTIPLE UPCOMING & ALREADY - ACHIEVED MILESTONES FOR NSI - 566 There are recently completed and near - term milestones for NSI - 566 across all 3 indications: I. Chronic Ischemic Stroke Phase I & II (n=31): Phase I trial demonstrated safety and preliminary evidence of clinical improvement in motor function from baseline levels. - Placebo - controlled study in China scheduled to complete 3Q 2020 II. ALS Phase I & II (n=30): demonstrated preliminary evidence of clinical benefit against historical data. - Pivotal study in the US in planning stages - FDA meeting March 2020 to provide feedback on pivotal study design & development plan III. cSCI Phase I (n=7): demonstrated safety, along with modest neurological improvements in some subjects. - Phase I completed 2019 Indication Preclinical Phase I Phase II Phase III Amyotrophic Lateral Sclerosis (ALS) Chronic Ischemic Stroke Chronic Spinal Cord Injury NSI - 566 STEM CELL PROGRAMS: PARTNERING BRIEF 1

 

 

MARKET OPPORTUNITY & KEY DATA BY INDICATION CHRONIC ISCHEMIC STROKE - MULTI - BILLION DOLLAR GLOBAL OPPORTUNITY Ischemic stroke is a leading cause of long - term disability and death worldwide . Ischemic strokes account for approximately 75 % of all strokes and occur as a result of an obstruction within a vessel supplying blood to the brain . Post - stroke motor deficits include paralysis or weakness in arms and legs and oftentimes are permanent . The National Stroke Association estimates there are 7 million stroke survivors in the US and literature reports indicate a total of > 80 million worldwide . Currently, there are no approved interventional therapies . Over 700 , 000 individuals suffer stroke in the US each year, and it is calculated that over 5 million people in China suffer stroke annually . There are no approved therapies to restore motor function, and therapeutic intervention is limited to rehabilitation . Conservatively, Seneca estimates at least 175 , 000 patients each year in the US could benefit from treatment with NSI - 566 . With a modest 10 % market penetration Seneca would reach 15 , 000 – 20 , 000 patients annually . This creates an attractive market opportunity in excess of $ 1 billion annually in the US alone . Globally, chronic stroke represents a multi - billion - dollar opportunity . NSI - 566 may provide an effective treatment for restoring motor deficits resulting from chronic ischemic stroke by creating new circuitry in the area of injury and by repairing and/or nurturing damaged neurons to improve function in patients . Seneca has completed a Phase I study and is currently conducting a placebo - controlled Phase II study at BaYi Brain Hospital in Beijing, China in 22 subjects with motor deficits due to ischemic stroke . Subject enrollment has been completed and topline data readout is expected in Q 4 of 2020 . SUMMARY OF THE PHASE I STUDY AND RESULTS : Subjects received one - time intracerebral injections of 12 , 24 , or 72 million cells adjacent to the area of the stroke lesion . Injections of NSI - 566 were found to be safe, and subjects showed a persistent improvement in motor function as measured by the motor scale of the Fugl - Meyer Assessment (Figure 1 , top) . When combined, subjects from the three cohorts of the trial showed a mean improvement of 16 points from their original baseline score on the Fugl - Meyer Motor Scale (FMMS) at 12 months after surgery . An improvement of > 10 points is seen as a meaningful clinical improvement . Subjects showed continued evidence of tissue regeneration in the area of the lesion two years after surgery (Figure 1 a, below, and Figure 1 b, next page) . FUGL - MEYER MOTOR SCORE Change from Baseline (+/ - SEM) - One - time administration: 12 - 72 million cells - Direct injections into lesion area of brain - 4 weeks of immunosuppression - Evidence of long - term graft survival (at least 2 years) - Evidence for tissue regeneration - Shows potential for motor improvement NSI - 566 STEM CELL PROGRAMS: PARTNERING BRIEF 2 Post Treatment (months, 0 - 12) Figure 1 a . Summary of Phase I trial in ischemic stroke . Subjects receiving cells showed a measurable and stable improvement relative to baseline in Fugl - Meyer motor scores for the 12 months following NSI - 566 transplantation (top right) . An improvement of 10 points or more in this index is considered clinically meaningful .

 

 

Figure 1b. The same subjects showed evidence of tissue regeneration in the infarct area over 24 months following the surgery (above). BASELINE 6 MONTHS 12 MONTHS 24 MONTHS KEY ATTRIBUTES THAT DIFFERENTIATE NSI - 566 FROM COMPETITORS BEING DEVELOPED TO TREAT CHRONIC ISCHEMIC STROKE: □ In preclinical studies NSI - 566 shows evidence of long - term survival in the ischemic brain and robust generation of neurons □ NSI - 566 survives for prolonged periods after transplantation to human CNS □ Results of Phase I trial suggest that NSI - 566 can induce regeneration of tissue in the area of the ischemic lesion and lead to stable improvement in motor function □ Controlled Phase II study underway with topline data readout expected later this year AMYOTROPHIC LATERAL SCLEROSIS (ALS) : - $ 1 B+ ORPHAN OPPORTUNITY ALS is a neurodegenerative disease that affects the cells in the brain and spinal cord that control voluntary muscle movement, the “motor neurons” . In ALS, nerve cells waste away or die and can no longer send messages to muscles . This eventually leads to muscle weakness and atrophy, leading to an inability to control voluntary movement . The condition is progressive, and when the muscles of the diaphragm are affected it becomes difficult or impossible to breathe . The average life expectancy of a person with ALS is two to five years from the time of diagnosis . There are currently two drugs in the US approved for treatment of ALS, though these provide nominal effectiveness . ALS is an orphan condition with 53 , 000 prevalent cases in the seven major markets (US, 5 EU and Japan) . In the US alone, the incidence of ALS is 5 , 600 people per year, and it is estimated that more than 20 , 000 Americans may be living with the disease at any given time . Seneca believes that approximately 65 % of newly diagnosed patients will be eligible for NSI - 566 . The potential launch of NSI - 566 is estimated to be prior to 2025 following a successful registration trial and will be focused on major neurosurgery centers . The company has identified qualified hospitals in the US that have sufficient combined capacity to treat 4 , 500 patients per year . Based on the recent launches of cell therapies for treating life - threatening diseases, including CAR - T therapies in oncology, the company estimates an attractive orphan market opportunity of greater than $ 1 B peak year sales . NSI - 566 STEM CELL PROGRAMS: PARTNERING BRIEF 3

 

 

The mechanism of action of NSI - 566 in ALS is likely to be trophic support of motor neurons, the neuronal population which is at risk in patients suffering from this disease . NSI - 566 has been evaluated in Phase I and Phase II safety studies in 30 subjects . Intraspinal transplantation of the cells was safe and well - tolerated, and evidence showed the cells take up residence within the spinal cord for prolonged periods after grafting . Post hoc analysis of combined data from both trials indicates that subjects receiving cells showed a decrease in the rate of decline of motor function (using the ALSFRS - R scale, an established clinical endpoint) compared to matched historical controls . SUMMARY OF THE PHASE I/II STUDIES AND RESULTS : The Phase I and II studies of NSI - 566 in ALS each enrolled 15 subjects and were designed to test safety and effects of dose escalation . Subjects received stereotaxic injections of up to 16 million cells to the cervical and/or lumbar spinal cord . The procedure was found to be safe and well - tolerated . Comparison of combined patient data from both trials (from ambulatory subjects without bulbar involvement) with that of historical controls indicates that NSI - 566 treatment may slow decline in ALSFRS - R scores in ALS patients (Figure 2 ) . KEY ATTRIBUTES THAT DIFFERENTIATE NSI - 566 FROM OTHER ALS PROGRAMS IN DEVELOPMENT: □ Potential to be first disease - modifying therapy in ALS based on preliminary evidence of efficacy in Phase I/II trial □ Only program in development for ALS that does not require repeat administration - dose is one treatment and done, and cells survive for years after implantation □ Provides human neural cells that stably integrate into the host spinal cord and may provide prolonged benefit, likely through trophic support of motor neurons ALSFRS - R SCORES: PHASE I/II VS. HISTORICAL CONTROLS TREATED CONTROL Mean change in ALSFRS - R 8 10 12 14 16 18 20 22 24 Month 0 2 4 6 Time after implantation (months) Figure 2 . Clinical outcome of combined patients from Phase I and II trials in ALS . In a post - hoc analysis, subjects receiving cells showed a significant improvement in ALSFRS - R scores relative to historical controls . ALSFRS - R is a clinical endpoint that reflects quality of life and is used routinely in clinical trials . The effect is stable at least 24 months after surgery . n = 10 vs 58 Δ = 7.78 p = 0.001 NSI - 566 STEM CELL PROGRAMS: PARTNERING BRIEF 4 - ALS Phase I/II combined data from ambulatory, non - bulbar subjects - NSI - 566 treated subjects showed evidence of clinical benefit compared to historical controls - Benefit persists for at least 2 years - Post - mortem analysis shows persistent graft survival in all subjects evaluated

 

 

CHRONIC SPINAL CORD INJURY (cSCI) - GLOBAL OPPORTUNITY As a truly unmet medical need, chronic spinal cord injury (cSCI) is an opportunity with significant potential . SCI is a long term, chronic and disabling neurological condition that may result from any trauma to the spinal cord, but most frequently occurs as a result of vehicle accidents and falls . The US prevalence of SCI is 249 , 000 - 363 , 000 with an annual incidence of ~ 17 , 000 new cases, and the WHO cites annual incidence of 250 , 000 - 500 , 000 new cases globally . Chronic SCI refers to the window after recovery has plateaued, beginning approximately 6 - 12 months after injury . cSCI disproportionally affects younger men, two - thirds of whom survive for at least 20 years . Patients are treated symptomatically during this time and have minimal prospects for functional improvement, leading to devastating effects on quality of life for patients and caregivers . There are currently no approved therapies to restore neurological function for these patients . Due to the large global incidence and gap in neurological treatment options, this creates a significant third market opportunity for NSI - 566 . NSI - 566 may provide an effective treatment for cSCI by “bridging the gap” in the spinal cord circuitry created in traumatic SCI and providing new cells to help transmit the signal from the brain to points at or below the level of injury . The company has recently completed a Phase I trial to test the safety and feasibility of NSI - 566 as a therapy for cSCI . SUMMARY OF PHASE I STUDY AND RESULTS : Subjects who had suffered thoracic (cohort 1 ) or cervical (cohort 2 ) spinal cord injury at least 12 months prior to surgery were administered 1 . 2 million cells by stereotaxic intraspinal injection . Neurological evaluation comprised recognized endpoints including ISNCSCI scores, pain scores, and electromyography (EMG), and subjects are being followed for up to 5 years . Improvements in sensory and motor function were apparent below the pre - surgery (baseline) level of injury in two of the four subjects in cohort 1 (improvement from T 8 neurological level to T 10 in subject 001 and from T 5 to T 6 in subject 010 ; Figure 3 ) . Figure 3. Clinical outcome of Cohort 1 from SCI trial. Two of four subjects experienced stable neurological improvements, as indicated by the change in diagnosed neurological level of injury. Subject Baseline 6 months 12 months 18 months 001 T8 T1 0 T1 0 T1 0 006 T7 - T7 T7 008 T2 - T2 - 010 T5 T6 T6 T6 KEY ATTRIBUTES THAT DIFFERENTIATE NSI - 566 FROM OTHER cSCI PROGRAMS IN DEVELOPMENT: □ NSI - 566 has the potential to be disease - modifying for cSCI □ NSI - 566 is capable of stably integrating into the patient’s spinal cord and surviving for years □ Preliminary evidence from Phase I trial suggests NSI - 566 may confer persistent neurological improvement □ Studies in non - human primates indicate NSI - 566 generates neurons that can integrate functionally into the CNS and bridge the gap between corticospinal tracts above and below the area of injury NSI - 566 STEM CELL PROGRAMS: PARTNERING BRIEF 5

 

 

CONTACT FOR BUSINESS DEVELOPMENT INQUIRIES: NSI - 566 STEM CELL PROGRAMS: PARTNERING BRIEF 6 CONCLUSION AND PARTNERING OPPORTUNITY NSI - 566 is a promising and unique partnership opportunity, driven by several key factors . It is distinguished from competitors by its unique mechanism of action as one of very few neural lineage restorative therapies in development . Further, strong evidence of safety along with preliminary evidence of clinical benefit in multiple indications provide a broad foundation for future partners or acquirers of the asset to advance into development . NSI - 566 is addressing unmet medical needs for significant populations worldwide in all three core indications : ischemic stroke, ALS and chronic spinal cord injury . In each indication this asset has demonstrated the potential for disease modifying efficacy . Moreover, NSI - 566 has been granted orphan drug designation for ALS by the US FDA and could be by approved for this indication as early as 2025 pending successful completion of a single pivotal study . The company is currently seeking global or regional partnerships or outright asset sale opportunities . By integrating the NSI - 566 asset with a partner’s development and commercialization capabilities and resources, it will be possible to accelerate development and approval and maximize the value of NSI - 566 in its core indications . SUMMARY OF PARTNERING PROCESS & TIMELINE Seneca is currently initiating a process for asset sale, out - license, global development partnerships or other transactions . The company’s current management team that will facilitate any form of transaction or partnership includes senior executives with extensive therapeutic R&D experience that have shepherded the NSI - 566 programs to date . Seneca is open to various structures : Investment, license/co - development, asset sale, or JV . The anticipated asset sale and out - license process with timelines is included below : - Q1 2020: Initial outreach to interested parties and initial due diligence - Q2 2020: Completion of diligence and soliciting term sheets by end of Q2 - Q3 2020: Transaction close, begin of technology transfer as required Business Development Contact: Sia Anagnostou Hibiscus BioVentures bd@hibiscusbio.com Seneca Biopharma, Inc. Contact: Kenneth Carter, PhD Executive Chairman Seneca Biopharma, Inc. kcarter@senecabio.com

 

 

Exhibit 99.02

 

Seneca Biopharma (NASDAQ:SNCA) Partnering Opportunities for CNS Diseases

 

 

SUMMARY OF ASSETS AND OPPORTUNITY SEEKING PARTNERSHIP & BUSINESS DEVELOPMENT OPPORTUNITIES ALS & SCI S T RO K E ALLOGENEIC OFF THE SHELF CELL THERAPY CLINICAL STAGE: ALS and Chronic Stroke (Phase II), Spinal Cord Injury (Phase I) ASSETS: First - in - class stem cell - based treatments for neurological diseases 2

 

 

o Regeneration of damaged neural tissue SENECA BIOPHARMA: NEURAL STEM CELL PLATFORM & IP SUMMARY PRODUCT o Allogeneic human neural stem cells: long - lasting therapeutic, requires temporary immune suppression o Committed neural lineage; CNS restricted; differentiate into functional neurons and glia o Stable, off - the - shelf product & manufacturing is scalable for commercialization MECHANISM OF ACTION: Functional Integration Of Human Neural Cells Into Host CNS o Neurotrophic protection and support (A) Regeneration of tissue adjacent to infarct site at 24 months after transplantation in human stroke subjects (B) Graft - derived neurons integrate, extend axons and form synaptic connections with healthy host neurons in non - human primate model INTELLECTUAL PROPERTY: Approximately 50 Issued and Pending US and Foreign Patents Providing Broad Coverage o Use of human neural stem cells for treating neurodegenerative diseases o Exclusive licensee of patents covering devices used to administer the Company’s stem cell therapies o Neuronal bridge across damaged circuits 3

 

 

Indication Preclinical Phase I Phase II Phase III Amyotrophic Lateral Sclerosis (ALS) Chronic Ischemic Stroke Chronic Spinal Cord Injury FDA MEETING: March 2020 CONTROLLED STUDY READOUT: Q4 2020 PHASE I STUDY COMPLETED: Q4 2019 NSI - 566 PIPELINE: ALLOGENEIC, OFF - THE - SHELF CELL THERAPY: 3 CNS INDICATIONS CHRONIC ISCHEMIC STROKE: Phase I & II (n=31) — Phase I trial demonstrated safety and preliminary evidence of improvement in motor function from baseline levels o Placebo - controlled study in China scheduled to complete 3Q 2020 ALS: Phase I & II (n=30) — Demonstrated preliminary evidence of clinical benefit compared to historical controls o Pivotal study in the US in planning stages o FDA meeting March 2020 to get feedback on pivotal study design and development plan CHRONIC SPINAL CORD INJURY: Phase I (n=7) — Evidence of stable improvement in some subjects o Phase I completed Q4 2019 4

 

 

ISCHEMIC STROKE: MULTI - BILLION - DOLLAR GLOBAL OPPORTUNITY WITH FEW COMPETITORS ISCHEMIC STROKE OPPORTUNITY o Stroke is the most common cause of disability in the United States, most common cause of death in China (CN); ~75% of stroke cases are ischemic stroke o Estimated stroke survivor population of 7MM (US) and 80MM (global) o Prevalent cases will grow to 8 million in China over 10 yrs o No approved restorative therapy for chronic stroke and treatment is symptom management o Conservative estimate of US eligible patients is 175K with 10% market penetration (15 - 20,000 patients annually) o There are no late stage stem cell trials underway focused on chronic stroke o One of only two restorative interventional therapies targeting chronic ischemic stroke, and the only therapy shown to stably integrate into human CNS o Demonstrated preliminary evidence of tissue regeneration and ability to stably restore motor function in Phase I trial 5 o Phase I completed o NSI - 566 treated patients showed preliminary evidence of clinical benefit o Controlled Phase II study underway in CN, readout Q4 2020 o Tiered cell banks produced under cGMP, manufacturing process scalable for commercialization, sufficient material generated for treatment of >1M patients o Breakthrough Therapy designation application being considered o Seeking to sell assets, out - license, or forge global partnerships for development STAGE OF DEVELOPMENT PLAN NSI - 566 ATTRIBUTES

 

 

6 Zhang et al., 2019, Stem Cells Transl. Med. 8(10): 999 – 1007 Engraftment over 24 Months: NSI - 566 produce neurotrophic environment that regenerates tissue at infarct site BA SE L I NE 6 MONTHS 12 MONTHS 24 MONTHS ONE - TIME ADMINISTRATION OF 12 - 72 MILLION CELLS: o Direct injections into the lesion area of brain o 4 weeks of immunosuppression o Evidence of long - term graft survival/tissue regeneration (≥ 2 yrs) o Preliminary evidence of stable motor improvement NSI - 566 AND CHRONIC STROKE: PHASE I DATA AT 12/24 MONTHS

 

 

ALS: $1B+ OPPORTUNITY FOR NSI - 566 ALS OPPORTUNITY o 53,000 prevalent cases in seven major markets (US, 5EU, Japan) o 5,600 ALS patients newly diagnosed in United States annually o 50% increase in developing World expected 2015 - 2040 o Limited treatment options with poor efficacy o US NSI - 566 addressable market: ~65% of newly diagnosed patients o Pricing from $300K to $500K in the US, similar to launched cell therapies o Potential to be the first disease - modifying therapy in ALS based on preliminary efficacy observed in Phase I/II studies o Only cell therapy program in development that provides cells of neural lineage that stably integrate into the host spinal cord o Only program in development for ALS that is not a chronic therapy. Dose is one treatment and done. o Approval is possible based on successful outcome of a single registration trial o Pivotal study in the US planned, feedback from FDA expected in March/April 2020 on study design & development plan o Seeking to sell assets, out - license, or forge global partnerships for development PLAN NSI - 566 ATTRIBUTES o Multi - site open label Phase II study completed o NSI - 566 treated patients showed preliminary evidence of clinical benefit compared to matched historical controls o Tiered cell banks produced under cGMP, manufacturing process scalable for commercialization, sufficient material generated for treatment of >1M patients o Orphan drug designation granted for treatment of ALS o Type C meeting scheduled with FDA to obtain feedback on trial design and development plan STAGE OF DEVELOPMENT 7

 

 

o NSI - 566 treated patients showed preliminary evidence of clinical benefit compared to historical controls o Autopsies of deceased trial participants revealed persistent graft in all patients evaluated: up to 2.5 yrs. after treatment AND 1.75 yrs. after immunosuppression ended NSI - 566 AND ALS: EVIDENCE OF EFFICACY COMPARED TO HISTORICAL CONTROLS TRE A TED CONT R OL Time after implantation (months) Mean change in ALSFRS - R ALSFRS - R Scores: Phase I/II vs. Historical Controls 8 ALS PHASE I & II (AMBULATORY, NON - BULBAR PATIENTS): EDARAVONE IS THE ONLY FDA APPROVED TREATMENT FOR ALS IN THE PAST 20 YEARS: o Reduced decline of ALSFRS - R by 2.5 pts over 6 mo. o Multiple cycles of IV infusion required

 

 

CHRONIC SPINAL CORD INJURY: 3 RD INDICATION PRESENTS FURTHER UPSIDE POTENTIAL SCI OPPORTUNITY o 17K cases in United States annually and between 250K - 500K globally o Managed symptomatically, little to no spontaneous improvement after initial stage o No therapeutic to restore neurological function, few active stem cell trials focused on cSCI (no late stage studies) o Provides potential for restoring function in cSCI patients o NSI - 566, which already has orphan drug designation in ALS, has a potential for Breakthrough Therapy designation o Demonstrated evidence of tissue regeneration and opportunity to partially restore motor function in NHP model o Preclinical data indicate NSI - 566 cells form connections with host neurons and ‘bridge’ area of injury 9 o Phase I trial completed Q4 2019 o Therapy was well - tolerated o Treatment is safe, some subjects show evidence of improvement o Seeking to sell assets, out - license, or forge global partnerships for development STAGE OF DEVELOPMENT PLAN NSI - 566 ATTRIBUTES

 

 

10 NSI - 566 AND SCI: EFFECT OF NSI - 566 IN MONKEY MODEL AND POTENTIAL BENEFIT IN HUMANS Rosenzweig et al., 2018, Nat Med. 24(4): 484 - 490 o Graft - derived neurons integrate, extend long processes and form synaptic connections with healthy host neurons o Grafts confer improvement in motor function NSI - 566 HAS A RESTORATIVE EFFECT IN A PRIMATE MODEL OF SUBACUTE SCI: SUBJECT BASELINE 6 MONTHS 12 MONTHS 18 MONTHS 001 T8 T10 T10 T10 006 T7 - T7 T7 008 T2 - T2 - 010 T5 T6 T6 T6 NSI - 566 SHOWS POTENTIAL FOR CLINICAL BENEFIT IN PHASE I TRIALS: o 2 of 4 subjects in first cohort experienced stable improvements in neurological level of injury (ISNCSCI) o Improvement detected at 6 months after surgery, consistent with MOA (functional integration, formation of neuronal connections to bridge injury) Curtis et al., 2018, Cell Stem Cell 22(6): 941 - 950

 

 

KENNETH CARTER, PH.D. Executive Chairman o Led public and private biotechnology companies as CEO and/or Chairman o Co - founder of Avalon, Noble, NeoDiagnostics, NexImmune, Iterion, and others o Extensive early - stage drug development experience o CEO of Avalon Pharmaceuticals 10 years including IPO, and 5 years as NASDAQ company o Strong R&D partnership record with Merck, Novartis, Sanofi - Aventis, MedImmune and others o Broad network and advisory board service. National BIO Board, Maryland Healthcare Dev. Corp. o Adjunct faculty member at Johns Hopkins University MATTHEW KALNIK, PH.D. Senior Advisor o Seasoned executive with drug discovery, development, licensing, and M&A leadership experience o Held/holds senior roles at Pharmacia/Pfizer, Daiichi - Sankyo, Nabi, Antidote Therapeutics o Senior leader/executive experience at large, medium and small biopharma (public and private) o Former Pharmacia/Pfizer head of strategic in - licensing unit o Leadership roles in successful R&D product development o Closed over $1 billion of transactions with greater than $100 million of upfront payments o Founded Antidote Therapeutics, Inc. and created first - in - class pipeline of nicotine blockers DANE SAGLIO Acting CFO o Leadership experience in finance, accounting, strategic planning, and business for multiple biopharma companies o CFO of several private and public companies: CASI, Helomics, RegenRx, others o Extensive experience in fundraising and management ranging from early - stage entrepreneurial enterprises through mature public companies o Well known for building teams, setting goals, maintaining focus and the ability to make and implement decisions o Deep experience in securities transactions, SEC compliance, corporate governance DAVID RECKER, M.D. Chief Medical Officer o Has overseen clinical development at Seneca/Neuralstem since 2017 o Has led many US and global clinical trials for small molecules, biologics, and cell therapy o Former head of Clinical Sciences with Takeda's Global Research and Development division, former CMO at Vericel Corporation o Broad experience in clinical development, regulatory affairs, medical and scientific affairs, pharmacovigilance, statistics and data management o Has implemented global clinical development strategies for several pharmacologic agents in multiple therapeutic areas THOMAS HAZEL, PH.D. SVP, Research o Senior leadership positions within Seneca/Neuralstem for 15 years o Has led platform technology development, preclinical research efforts, and CMC initiatives for Seneca/Neuralstem in the US and its subsidiary in China o 25+ years of biopharma R&D experience o Extensive experience in technology transfer, translational research, and product development 11 SENECA MANAGEMENT TEAM

 

 

PROMISING PARTNERING OPPORTUNITY o First - in - class stem cell - based treatments for neurological diseases o Unmet medical needs in CNS diseases: ALS, chronic stroke, chronic spinal cord injury o Strong fundamental science and technology platform, significant development to date o Existing global academic partnerships & footprint o Several upcoming clinical milestones 12

 

 

TRANSACTION SUMMARY & TIMELINE SUMMARY o Initiating process for asset sale, out license, global development partnerships o Open to various structures: Investment, license/co - development, asset sale, or JV TIMELINE o Q1 2020: Initial outreach to interested parties and initial due diligence o Q2 2020: Completion of diligence and soliciting term sheets by end of Q2 o Q3 2020: Transaction close, beginning of technology transfer as appropriate 13

 

 

THANK YOU CONTACT INFORMATION: Kenneth Carter, PhD Executive Chairman k c arter @ senecabi o .com 14