VDP-47 [Assessment]: Immunis Biomedical

One-liner: Overview of Immunis Biomedical, a phase 1/2a clinical stage biotech company, developing a secretome product from human immune system progenitor cells.

This proposal is based on the supporting documents provided by Immunis, as well as questions and answers to their team, and senior reviews.
If this goes on-chain, the VITA token holders will ratify the WG’s assessment via a decentralized vote

Longevity Dealflow WG team

Scientific & IP evaluation: Sebastian Brunemeier, Diane Seimetz, 2 anonymous biotech entrepreneurs & researchers

Shepherd: Laurence Ion

Other squad members: Tuan Dinh

Sourced by: Laurence Ion

Project lead: Dr. Hans Keirstead

Simple Summary

IMMUNIS has generated the first secretome product from human immune system progenitor cells, that has been shown to be effective in multiple manifestations of ageing, slowing the process of ageing, enhancing health while ageing, and reversing age-related deficit in multiple organ systems. IMMUNIS has recently been awarded a Phase 1/2a clinical trial to test their first-of-the-kind product to treat ageing symptoms in humans. IMMUNIS is raising Series A to fund company operations while executing Phase 1/2a and Phase 2 clinical trials, for a total duration of about 24 months, until Phase 3 approval. VitaDAO will be allocated a proportion of the Series A shares.

Problem

Immune system progenitors secrete factors that keep the immune system healthy. As you age, your immune system progenitor content decreases and their secreted factors are fewer, causing degeneration in every system in your body.
IMMUNIS is targeting age-acquired immune deficiency.

Opportunity

IMMUNIS has generated the first secretome-based treatment (termed STEM) from human immune system progenitor cells, which has been shown to be effective in multiple manifestations of ageing. IMMUNIS’s secretome includes multiple effectors, including transcription factors, growth factors, angiogenic molecules, lipid mediators, nucleic acids, cytokines, chemokines, hormones and extracellular vesicles and can serve multiple biological functions, including cell survival and proliferation, anti-apoptosis, cell contractility, migration, angiogenesis, anti-inflammation, immunomodulation and homing of resident stem cells.

Independent studies in mice conducted by University of Utah researchers (Reversal of deficits in aged skeletal muscle during disuse and recovery in response to treatment with a secrotome product derived from partially differentiated human pluripotent stem cells - PMC) and independent immunology laboratories confirmed that IMMUNIS product had anti-ageing effects including

  • Prevention of age- and disuse-associated decrease in muscle mass, strength and fiber cross sectional area
  • Prevention of age- and disuse-associated increase in muscle fibrosis
  • Increased rodent muscle cell growth
  • Increased human muscle myotube area and myonuclear fusion in a dose-dependent manner
  • Decreases age- and disuse-associated increase in inflammation and clinical disease
  • Reduced neuroinflammation, demyelination and CNS degeneration
  • Prevents age- and disuse-associated increase in arterial stiffness
  • Increased the effectiveness of the adaptive immune system

The initial indication is muscle atrophy based on results of several focus group meetings of domain experts. Muscle deterioration and weakness is a result of immobilization, disease and aging. One indication with 2 of these 3 causes of muscular atrophy is knee osteoarthritis-associated muscle atrophy, which combines an acute muscular immobilization with age-related muscle atrophy, resulting in profound acute muscle atrophy. Muscle wasting associated with age and immobilization causes a substantial decrease in muscle strength, size and ability of muscle movement. It is caused by a lack of activity, several diseases and in every person as a result of aging (sarcopenia). Most individuals begin to lose muscle mass after the age of thirty, adversely affecting levels of activity and quality of life.

Global muscle wasting disease market is $4-5B annually.

Investigational New Drug (IND) enabling studies showed that the product did not cause adverse changes to blood, urine, behaviour, body weight, food consumption, histopathology, and immune response. IND application was approved in Q1, 2022.

The US FDA has approved pre-clinical safety studies as part of the full and formal approval of Phase 1/2a clinical trial. The pre-clinical safety studies were conducted by a third party blinded GLP research facility as per US FDA policy.

Experimental plan

IMMUNIS plans to complete Phase 1/2a/Phase 2 trials in 2022. The initial indication is muscle atrophy based on results of several focus group meetings of domain experts. The trial will focus on prevention of muscle atrophy but Immunis will also measure reversal.

The clinical site is UC Irvine Alpha Stem Cell Clinic.

The following has been approved by the US FDA for the fully approved Phase 1/2a study.

Up to 18 participants will receive twice weekly intramuscular (im) administration of IMM01-STEM for 4 weeks in up to 3 dose cohorts:

  • Cohort A, IMM01-STEM 225μg;
  • Cohort B, IMM01-STEM 450 μg; and
  • Cohort C, IMM01-STEM 900 μg.

Each cohort will include 3 to 6 participants.

For each participant, the expected maximum duration of participation will be approximately 20 weeks, consisting of the following:

• Screening Period: up to 4 weeks, ending on Day -1

• Treatment Period: approximately 4 weeks (Day 1 through Day 25)

• SFU Period: approximately 3 months (Day 26 through Day 112)

The primary objective is to evaluate the safety of IMM01-STEM treatment in study participants with muscle atrophy related to KOA

IP Roadmap

IMMUNIS has an intellectual property portfolio, and has recently been awarded a Phase 1/2a clinical trial to test the product in humans.

Team

CEO and Chairman: Dr. Hans Keirstead has built and sold 4 other companies in this sector, all at high returns to investors. Dr. Keirstead is an internationally known cell therapy expert who has led therapy breakthroughs including platform treatments late-stage cancers, spinal cord injury, multiple sclerosis, motor neuron diseases, rheumatoid arthritis, retinal disease and skin health. He is also an expert in cellular manufacturing and international cell therapy policy and law and long time advisor to several governments on biomedical policy. Dr Keirstead has over 100 peer-reviewed publications; over 150 students mentored. See here for Dr Keirstead’s bio: Hans S. Keirstead, Ph.D. – AIVITA Biomedical

CSO: Tom Lane, PhD is a Professor at UC Irvine. Dr Lane has been working in evaluating mechanisms governing neuroinflammation in response to infection, injury, or autoimmune-induced neurologic disease. After completing his Ph.D. research in Microbiology and Immunology at the UCLA School of Medicine, he did his postdoctoral work in neurovirology at the Scripps Research Institute in La Jolla, CA. Dr. Lane joined the Biological Sciences faculty at UC Irvine in 1998 where he is now a Chancellor’s Professor of Neurobiology & Behavior. Dr. Lane has served as Director of the Multiple Sclerosis (MS) Research Center and Associate Director of the Institute for Immunology. Lane was awarded a National Multiple Sclerosis Society (NMSS) Collaborative Center Award as well as a California Institute for Regenerative Medicine (CIRM) Early Translation Award dedicated to exploring the therapeutic potential of neural stem cells in treating human demyelinating diseases with a primary focus on MS. For a complete bio of Dr Lane, please go to Dr. Tom Lane – The Lane Lab

SAB Chairman: Gabriel Nistor, MD has been involved in many clinical research projects in numerous fields and conducted seminal research at University of California, Irvine between 2000 and 2010. He has broad, multidisciplinary knowledge and skills in all science areas, with primary expertise in the biological and medical fields.

He is a world leader in stem cell and spinal cord injury research and has developed many novel methods and procedures to the advancement of those fields. In 2004, under the direction of Hans Keirstead of the Keirstead Research Group at UC Irvine, Dr. Nistor successfully co-developed a human embryonic stem cell derived treatment for acute spinal cord injuries in rats. That treatment was approved by the FDA for clinical trials in humans with acute spinal cord injuries. The trial, currently in progress sponsored by Asterias Biotherapeutics, marks the first human embryonic stem cell trial ever approved in the U.S.

Prior to joining AIVITA Biomedical, Dr. Nistor served as Vice President, Research at Caladrius Biosciences. There he created a quality-by-design environment compliant with modern cGMP practices to support the research, development and manufacturing troubleshooting of a phase III clinical trial for advanced stage melanoma using autologous tumor initiating cells and autologous dendritic cells. For a complete bio of Dr Nistor, please go to Gabriel Nistor, M.D. – AIVITA Biomedical

Financing

Series A: $10M - Preferred Stock; 8% interest; pre-money valuation of $20M

Led by a US-Japan cross-border venture capital firm focused on therapeutics, with US$6M committed

In Dec 2021, Immunis completed a $2M Convertible Note which converts to the Series A Preferred Stock, with 8% interest, $17M pre-money valuation

Series A funds will support general operations of the company while we run a Phase 1/2a and Phase 2 clinical trial, for a total duration of about 24 months, until Phase 3 approval. The vast majority of biotechnology assets that are awarded Phase 3 status are purchased for abut $300-600M. The Series A has a pre-money valuation of $20M.

The budget for the Phase 1/2a clinical trial is $980,000. The budget for the Phase 2 is $2.8M. The $10M First Closing of the Series A was completed on June 1st, 2022. The $2M Second Closing will be completed in 120 days, on November 1st, 2022, at the latest. Thus, Immunis will have enough money to conduct 2 Phase 2 clinical trials and get to Phase 3 approval, and then have over 2 years of cash in the bank while partnering/sale is being sought.

Strengths

  • Independent studies confirming that the product has effects on ageing markers
  • IND-enabling safety studies confirmed that the product did not produce adverse effects
  • Experienced CEO with a lot of experience leading a therapy through clinical studies and successful exits
  • Potential expansion to a large number of age-related indications
  • FDA approved Phase 1/2a clinical trial

Risks

  • Level of commitment from the founder given his prior successful exits - this is mitigated by a Stock Restriction Agreement with Dr. Hans Keirstead as part of the Series A
  • The usual risks associated with early stage drug development. Not all drugs that have been shown to work in animal models work in humans. Immunis considers this a very low risk as their product is a naturally occurring human immune secretome that all humans are responsive to, but have less of as they age. The risk is also decreased by
    • (i) the very high efficacy signal of the product in multiple animal models,
    • (ii) the very high efficacy signal of the product on human muscle cells in a dish, and
    • (iii) track record of the Founder and his team.
  • Manufacturing risk. Immunis considers this is minimal, as the team is one of the leading, or the leading, human stem cell manufacturer in the world. Immunis does not expect to have any problems in manufacturing. Possible pitfalls are the development of an acceptable potency assay during Phase 3 (common to every biologic in Phase 3). There’s no manufacturing risk for the Phase 1/2a and 2 Phase 2 clinical trials as the products have been produced for these studies.

Vote:

Here we’ll vote if this should go on-chain, along with the final assessment from the Senior Reviewers, and the community as a whole.

If it succeeds here, the VITA token holders will ratify the WG’s assessment (positive or negative) via a decentralized vote.

  • Agree
  • Agree with revisions (please comment)
  • Disagree

0 voters

Added a few more details based on the answers to our followup questions

You mentioned that exits ranged from $300-600M for " the vast majority of biotechnology assets that are awarded Phase 3 status". Is this specifically for single assets in the indication of interest (muscle wasting)?

I’d also be interested in a little bit more on the scientific risk here. What is the probability of success for a therapeutic in this indication? What has been explored in the past? Why did they choose this indication beyond KOLs telling them to do it? Is there an established endpoint that they can leverage for Ph. 2b and 3 that has been used for a previous approval?

2 Likes

I am intrigued by applicability to cachexia in the oncology setting. Is there additional information on the GLP tox protocol agreed to with FDA? A major concern of mine is lack understanding at the mechanistic level what would be driving the efficacious effect, and of course how to interpret off target effects without understanding MOA.

These STEM cells would have to be harvested from each patient - i.e., an autologous approach?

Also intersted to learn how/where they can run a Ph1 for <$1M USD and a Ph2 for $2.8M USD.

Would be interested to see a pitch deck and understand what other investors are potentially participating. How much cash has gone into the company to arrive at the $20M valuation.

Thanks!

1 Like