Our novel drug candidate blocks the cis-interaction between Repulsive Guidance Molecule A (RGMa) and Neogenin and disrupts Neogenin incorporation in lipid rafts. This candidate’s therapeutic interaction promotes cell survival and axonal regeneration in severe medical conditions including retinitis pigmentosa, multiple sclerosis, ischemia (e.g., stroke), and spinal cord injury. The ideal strategy to ameliorate CNS damage is through promoting both survival and axonal regeneration.

UNMET NEED
4IG targets the neuronal regeneration pathway that has not yet been drugged. Multiple disease indications are implicated including Retinitis Pigmentosa, Stroke, Spinal Cord Injury, and Multiple Sclerosis.

INNOVATION
Biologic therapeutic comprised of ~400 amino acid, soluble Ig extracellular domain of Neogenin

Dual mechanism of action by:
1.binding (Repulsive Guidance Molecule a (RGMa) and
2. inhibiting Neogenin incorporation in lipid rafts

Potential therapeutic for preventing neuronal death in multiple human indication through direct effect at neurons and indirect effect through reducing permeability of Blood Brain Barrier

APPLICATION/UTILITIES
Biologic therapeutic targeting diseases involving neurodegeneration; multi-disease potential (one product).

INVESTMENT & OBJECTIVES
 $5-7M for IND enabling studies.

COMPETITIVE ADVANTAGE
Closest competitors are elezanumab and unasnemab, which are under development from AbbVie Inc and Mitsubushi Tanabe Pharma Corp, respectively.   Both elezanumab and unasnemab  are intravenously administered, α-RGMa monoclonal antibodies. Elezanumab is under Phase II development for the treatment of relapsing-remitting multiple sclerosis, acute ischemic stroke, primary and secondary progressive multiple sclerosis and spinal cord injury. Unasnemab is under Phase II development for the treatment of spinal cord injury and Phase I development for the treatment of Tropical Spastic Paraparesis.

Whereas elezanumab and unasnemab have a single mechanism action, 4Ig both binds RGMa and inhibits the incorporation of Neogenin in lipid rafts.

‍MARKET SIZE
·   Global stroke therapy market expected to grow to over $US10B by 2027

·   Global Multiple Sclerosis therapy market expected to grow to over US$29B by 2030

·   Global Retinitis Pigmentosa therapy market expected to exceed US$2B by 2030

·   Global spinal cord injury treatment market expected to reach almost US$3B by 2027

IP PORTFOLIO
Two patent families describing methods, with 6 issued patents and 1 issued patent.

CURRENT MANAGEMENT TEAM
‍n/a

CURRENT READINESS LEVEL
Proof of concept/pre-clinical.‍

EIR STATUS
‍Recruitment in progress.

‍SCIENTIFIC FOUNDER(S)
Dr. Philippe Monnier, Senior Scientist, Krembil Research Institute, an accomplished researcher focused on uncovering the role of extracellular proteins in the developing and regenerating CNS.

Porphysomes are a platform technology based on lipid vesicles made of nanoparticles called porphyrin, with versatile applications including cancer imaging, phototherapy, and drug delivery. Porphysomes can be loaded with chemotherapeutic agents and have properties that make them ideal as a photothermal therapy chemical. Porphysomes are capable of fluorescence, or harnessing and releasing laser energy. They also accumulate in cancer tissue. Accumulation in cancer tissue and concomitant release of photoenergy means they can ablate malignant tissue. Additionally, porphysomes can be modified with heavy metals to facilitate PET imaging. Porphysomes can be used to target lung, ovarian, prostate, endometrial, head/ & neck and pancreatic cancers.

‍UNMET NEED
‍Photodynamic therapy was first approved by the FDA in 1995.  While the therapy can be curative in early-stage cancer, it remains underappreciated partly due to side effects caused by the photosensitizer agents.  Porphysomes represent a new generation of photosensitizers with minimal expected side effects and additional capabilities.   

‍INNOVATION
Porphysomes are a patented porphyrin-lipid technology. The porphyrin component of a porphysome delivers the photosensitizing property while the lipid component provides additional functional capabilities. These multi-functional characteristics provide the opportunity to design agents for a variety of applications.

‍APPLICATION/UTILITIES
‍Porphysomes can be designed as a treatment agent, delivering a drug payload or with a radioactive tracer for diagnostic imaging. Current iterations target lung, pancreatic, head/ neck, endometrial, ovarian and prostate cancers

‍INVESTMENT & OBJECTIVES
$20M USD, for the purpose of: 

-        Completion of first-in-human safety study

-        CMC, GMP and regulatory for Phase 1b/2a theranostic multi-indication study

-        Phase 1b/2 theranostic study with three to four disease indications

‍COMPETITIVE ADVANTAGE
‍New generation of photosensitizing agent with multi-functional capabilities. Patented technology with a large set of preclinical validation to-date.  Plan for first in human study is underway. Opportunity to expand an underappreciated treatment modality with proven potential curative effect on certain early-stage cancer indications.

‍MARKET SIZE
Estimated market value of photodynamic therapy is US $3-5B. CAGR is estimated at 4-8%.

IP PORTFOLIO
Three patents cover the composition of porphysomes, usage in photothermal therapies and photoacoustic imaging as well as different porphysomes with alternative lipid conjugates. Several patent filings are in progress covering porphysome modifications that enhance uptake into cancer cells and enhance ability to carry chemotherapeutic agents (e.g. paclitaxel)

‍CURRENT READINESS LEVEL
‍Entering first in human testing.

‍SCIENTIFIC FOUNDER(S)
Dr. Gang Zheng - Senior Scientist and Associate Research Director, Princess Margaret Cancer Centre

Porphysomes are based on ground-breaking research by Dr. Gang Zheng, a world-renowned expert in nanomedicine and Associate Research Director at the Princess Margaret Cancer Centre. Named contributor to the “top 10 cancer breakthroughs of 2011” by the Canadian Cancer Society for his work on harnessing porphysome nanotechnology in the fight against cancer, Dr. Zheng’s nanotechnology platform is the foundation for this new venture. For more information: http://zhenglab.utoronto.ca/

Despite significant progress in CPR methods in recent decades, survival following sudden cardiac arrest due to Ventricular Fibrillation (VF) and subsequent advanced life support has not dramatically improved. The on-market, off-patent drug Dantrolene has been safely used in clinical practice with few side effects for many years. Research at UHN has shown that Dantrolene decreases the number of refibrillations required and substantially improves cardiac contractility and Return of Spontaneous Circulation (ROSC) following defibrillation. Dantrolene administration thus has significant potential to improve survival following VF arrest. This technology also has potential applications in the treatment of chronic heart failure and chemotherapy-induced cardiotoxicity.

‍UNMET NEED
Ventricular Tachycardia (VT) is a common cause of sudden cardiac death. Implantable devices to monitor and correct the irregular heart rhythm can save lives, but this strategy is invasive and costly, and it does not cure the lethal condition. Radiofrequency ablation is an alternative treatment, but it has a high failure rate. Treatment with doxorubicin although very useful in many cancers, can lead to heart damage that reduces the quality and quantity of life that a cancer survivor can expect.

INNOVATION
Dantrolene is traditionally prescribed as a muscle relaxant and has been in clinical use for decades. Research at UHN has demonstrated that Dantrolene can also suppress life-threatening irregular heartbeats. Analysis of clinical data has indicated that long-term use of Dantrolene as a muscle relaxant is safe and does not exert negative influences on the heart.  Further, the use of dantrolene during chemotherapy with doxorubicin can reduce the possibility of future cardiomyopathy. 

APPLICATION/UTILITIES
·        Acute treatment of Ventricular Tachycardia (VT)

·        Treatment of treatment of chronic heart failure  

·        Prophylaxis of chemotherapy induced cardiotoxicity

‍INVESTMENT & OBJECTIVES
$5M - $15M required to: 

·        Develop a rapid administration formulation of Dantrolene. 

·        Assess the pharmacokinetics (PK) of rapid administration Dantrolene formulation in a large animal model. 

·        Assess human PK of reformulated Dantrolene in a FDA-approved centre. 

·        Demonstrate the effects of reformulated Dantrolene on the frequency of PVCs of patients suffering from idiopathic PVCs.

COMPETITIVE ADVANTAGE
First-line therapies, such as β-antagonists and Ca2+ channel blockers, are often ineffective for the treatment of VT.[JA6]  While Flecainide is effective, its concurrent blockade of sodium channels can also promote ventricular arrhythmia. Though effective in inactivating arrhythmogenic tissues, cardiac ablation is an invasive procedure with a high failure rate.  

‍MARKET SIZE
The global market for ventricular tachycardia [JA7] diagnosis and treatment was valued at US $12.5 Bn. in 2021 and . is expected to grow at a CAGR of 5.26 % to US$17 B. by 2027. Doxorubicin currently sells US$1.3B annually and its use is increasing despite substantial risk of cardiotoxicity. The success of an abatement for cardiotoxicity as well as potentially selling as much as doxorubicin may increase the demand for doxorubicin-based chemotherapy.

IP PORTFOLIO
Two patent families, including issued patents in EU and US, covering multiple applications of the technology.

‍CURRENT READINESS LEVEL
Pre-clinical technology, requires demonstration in clinical trial. 

EIR
Nigel deGruyther

Nigel deGruyther is a pharmacist and entrepreneur with experience in drug repositioning efforts and venture capital and the former Head of Business Development at Cynapsus Therapeutics.

‍SCIENTIFIC FOUNDER(S)
Dr. Kumaraswamy Nanthakumar is a clinical cardiologist and cardiac electrophysiologist at UHN and a Senior Scientist at the Toronto General Hospital Research Institute, with a focus in cardiac arrhythmia modulation and stabilization of RyR2. He is also Professor of Medicine at the University of Toronto.

‍

With this new venture, ground-breaking scientists at the Krembil Brain Institute are combining efforts – synergizing their insights and deep knowledge in neuroinflammation biology and  special domain expertise in central nervous system drug design to drive innovation across a pipeline of neuroinflammation drug projects .

‍UNMET NEED
Neuroinflammation is a key contributor to most neurodegenerative disorders. Gliachem offers a portfolio of promising therapeutic targets and advanced novel small molecule drugs that prevent neuro-inflammation.

INNOVATION
Drug candidates with novel features:  

-        First-in-class brain-penetrant small molecules (based upon design considerations including novel blood brain barrier score [BBBS] and animal in-vivo data) 

-        Modulation of novel pathways and targets that are present on/in glia and neuronal cells

-        Favourable pharmacology attributes for CNS treatments,including:

·        Physico-chemical properties

·        Moderate to low nM potency on the targets 

·        Not containing structural alerts

APPLICATION/UTILITIES
Four drug development programs targeting unaddressed neurodegenerative disorders of the central and peripheral nervous system.  

INVESTMENT & OBJECTIVES
$10M to be used for:

·        lead identification and,

·        IND-enabling studies for prioritized candidates

‍MARKET SIZE
The treatment of central nervous system (CNS) disease is a market growing at 9.4% CAGR to US$166.5B by 2029.

IP PORTFOLIO
·        Method patent issued and composition patent allowed

·        Additional composition and method patents pending

·        Additional composition patent applications pending lead optimization

CURRENT READINESS LEVEL
‍Lead identification via analogues; pre-clinical

‍EIR
Vanessa Williamson

‍SCIENTIFIC FOUNDER(S)
This new initiative is a collaboration among distinguished researchers at the Krembil Brain  Institute:

-        Dr. Donald Weaver, a neurologist and medicinal chemist who is a serial founder and has several neurology compounds in preclinical / clinical development

-        Dr. Mark Reed, an experienced industry veteran in neurology drug discovery who leads UHN’s Centre for Medicinal Chemistry and Drug Discovery

-        Dr. Jeremy Sivak, an expert on retinal biology and drug delivery (ex-Novartis)

-        Dr. James Eubanks, a noted researcher in epigenetic and mitochrondrial diseases of the brain

‍

DNT Therapeutics offers an allogeneic double negative T cell therapy platform that is a viable ‘off-the-shelf’ T cell based therapeutic.

UNMET NEED
Autologous Cancer Antigen T cell therapy (CAR T) has generated substantial excitement and has been shown to eradicate advanced leukemias and lymphomas. However, autologous use has limited their utility and a substantial fraction of treated patients are unresponsive or relapse or ineligible for treatment. CAR based allogeneic therapeutics would address the limitations of current CAR Ts and impact tumor eradication in patients that are not treatable by  current autologous CAR Ts.

INNOVATION
A novel subset of mature double negative T cells (DNTs) that are CD3+, CD4- and CD8- double negative cells. They have off-the-shelf T cell therapy attributes and are suitable for CAR engineered T cell therapy. DNTs have demonstrated a significant differentiation from competitor allogeneic cell therapy platforms in the areas of safety, suppression of GvHD, persistence and promising efficacy.

APPLICATION/UTILITIES
The therapy targets relapsed/refractory and relapsed allo-transplanted AML patients. Engineered DNTs will be pursued as a platform technology focused on creating a pipeline to address high unmet medical need and provide a competitive advantage in the treatment of various cancers including solid tumors.

INVESTMENT & OBJECTIVES
‍Capital raise of $10-15M will enable completion of an investigator-initiated Phase 1 AML clinical trial at Princess Margaret Cancer Centre and help to build an engineered allogeneic T cell cancer therapy portfolio of two to four assets.

COMPETITIVE ADVANTAGE
Clinically de-risked – demonstrating safety, a defined starting dose and dose frequency. A moderate clinical response in AML was observed. The key competitive differentiation is a true allogeneic T cell platform that has a simplified CMC process and is more efficiently scalable. DNTs also demonstrate superiority to competitor allogeneic platforms (e.g., gamma delta T cells and NK cells) with regards to tumor efficacy, persistence, and safety in preclinical animal models.

‍MARKET SIZE
The global T cell therapy market is expected to grow to over US$25.6 Billion by 2027.

DESCRIPTION OF IP PORTFOLIO
Mature portfolio comprised of two families, covering a breadth of applications and utilities. Second family encompasses 8 patents including engineered DNTs.

CURRENT READINESS LEVEL
The lead un-engineered DNTs are poised to initiate Phase 1 studies in a Health Canada approved Phase 1 clinical trial. Three CAR-DNTs have demonstrated preclinical proof-of-concept and poised to generate a differentiated CAR-DNT pipeline

CURRENT MANAGEMENT TEAM
Kuldeep Neote – CEO
A former senior executive with Eli Lilly and Johnson & Johnson, Dr. Neote began his career as a discovery scientist, initiating the chemokine receptor drug discovery platform that led to the discovery and further development of several clinical candidates at Pfizer Inc. He spent the latter part of his pharma career on external innovation, NewCo value creation and start-ups, JLABS incubator companies and venture initiatives.
‍Jongbok (JB) Lee – Interim CSO

SCIENTIFIC FOUNDER(S)
Li Zhang , Senior Scientist, Toronto General Hospital Research Institute (TGHRI)
‍Jongbok (JB) Lee, Senior Scientific Associate at UHN, Immunologist

Immunotherapies are showing promise for the treatment of cancer, including approaches that target cancer cell antigens. However, despite the presence of these antigens, tumors are not readily recognized and eliminated by the host—resulting in cancer development and progression. Interleukin-12 (IL-12) forms the platform for Vela. IL-12 is a cytokine that has powerful effects on the immune system. Direct injections of IL-12 as a leukemia therapy have illustrated the potential of this approach in clinical trials, although outcomes were modest and toxicity was evident at required levels. Research at UHN has demonstrated that IL-12 delivered via transduced cancer cells has a marked anti-cancer effect while dramatically reducing IL-12 dosage required for therapeutic impact, potentially with reduced toxicology.

UNMET NEED
IL-12 has long been recognized as one of the most potent cytokines in mediating antitumor activity in the immune system.  However, the application of this agent to cancer treatment has met with great difficulty.  Systemic and some targeted delivery of IL-12 failed to show sustained antitumor responses and were associated with significant toxic side effects. 
VELA has developed a lentivirus-based IL-12 cell therapy that minimizes undesirable side effects while providing sustained therapeutic effect to the target. Acute myelogenous leukemia (5 year survival rate of 26%) and ovarian cancer (5 year survival rate of 45%), which have low survival rates, are being targeted by VELA.

INNOVATION
VELA has invented a lentivirus cell therapy that delivers IL-12.  By transforming patient-derived cancer cells with IL-12 and then delivering back to the patient, VELA is able to precisely calibrate the amount of IL-12 to use and train the immune system to provide a sustained treatment effect.

APPLICATION/UTILITIES
IL-12 mediates antitumor response in a variety of cancers. Potential applications include both liquid and solid tumors. Lead applications under development for Autologous Acute Myeloid Leukemia (AML) and ovarian cancer.

INVESTMENT & OBJECTIVES
$20 Million USD to be used for:

·        Completion of Phase I Trial in AML 

·        Conduct Phase I Trial in Ovarian cancer

·        Complete pre-clinical development of dual cytokine therapy

·        Develop off-the-shelf therapeutic product

COMPETITIVE ADVANTAGE
The Vela approach allows the generation of high local concentrations near cancer cells, with very low, non-toxic systemic levels of IL-12.  This method also generates ‘memory’ in the immune system and provides a sustained effect.  In addition to IL-12, other cytokines or biological agents can also be co-administered to complement additional therapeutic modality.

‍MARKET SIZE
·   The Acute Myeloid Leukemia (AML) market is projected to reach US $976M by 2026 with a CAGR of 12.6%.

·   The ovarian cancer market is projected to reach US $3.5 billion by 2025 with a CGAR of 19%.

IP PORTFOLIO
Two patent families including issued patents covering multiple applications of the technology

CURRENT READINESS LEVEL
Clinical stage technology (Phase I trial in AML underway)‍

EIR STATUS
‍Actively recruiting

‍SCIENTIFIC FOUNDER(S)
Dr. Christopher Paige is a Senior Scientist at Princess Margaret Cancer Centre of UHN. Additionally he is a scientific founder and board member of the NASDAQ listed AvroBio Inc. and former Vice President, Research (1997 to 2016)

‍

Paradox Immunotherapeutics is an orphan drug platform company dedicated to the creation of antibody therapies for the treatment of rare diseases caused by protein misfolding. The company was founded by former UHN scientists with a history of substantial success in the selective targeting of misfolded proteins with monoclonal antibodies. One of their success stories includes their design and development of an antibody at UHN which was out licensed to Prothena Biosciences and resulted in a $1.2B acquisition deal with Novo Nordisk (2021).
‍

Paradox has developed a platform technology which can be applied to the design of therapeutic antibodies for multiple protein misfolding diseases. Paradox’s unique approach includes capitalizing on experience in the field of protein misfolding research; leveraging  this ground-breaking lead identification and validation platform provides a competitive edge to overcome traditional challenges that previously made these diseases deemed incurable. 
‍

For more information: https://www.paradoximmuno.com / https://youtu.be/2tCpe28Ok9Q

‍UNMET NEED
The challenge with treating protein misfolding diseases is designing therapeutics which target the often-scarce disease-causing forms of a protein, while avoiding the abundant, healthy proteins which perform important roles in the human body. Because of this, many protein misfolding diseases are very difficult to manage and are currently thought of as incurable. This includes the protein misfolding disease AL amyloidosis, which causes multi-organ failure. There is an urgent unmet medical need for non-invasive therapies that directly remove lethal deposits from organs with minimal side effects.

INNOVATION
Paradox has developed a proven drug design platform that successfully enables the identification and development of specialized antibodies that selectively target problematic/misfolded proteins while leaving healthy proteins in the body untouched. A challenge many companies have struggled with, this is an area in which Paradox excels.

APPLICATION/UTILITIES
‍To date, the Paradox team has used their first-of-its-kind platform to trailblaze therapeutic developments in various protein misfolding disease indications: AL amyloidosis (associated with multiple myeloma) and is now expanding to kidney (i.e. ALECT2 amyloidosis) and neurodegenerative diseases.

INVESTMENT & OBJECTIVES
$18M USD in equity financing to:

·        bring its lead candidate LX-96 to IND filing,

·        expand its platform and pipeline to two new validated clinical candidates (LX-97 & KX-99), and

·        solidify its position as the global leader in protein misfolding therapeutics.

COMPETITIVE ADVANTAGE
‍The Paradox Platform can predict unique features on target proteins that are only present in diseased forms, allowing the design and development of therapeutic antibodies against them. ‍

‍MARKET SIZE
Approximately 30,000-45,000 patients in the USA and EU suffer from AL amyloidosis, with a projected US market of $5.1B in 2032. AL amyloidosis is only one of many protein misfolding diseases and Paradox's primary point of market entry. With expansion of Paradox’s therapeutic portfolio, they aim to become a major player in the emerging market of protein misfolding.

IP PORTFOLIO
‍Family of patents comprising antibody compositions. 

CURRENT MANAGEMENT TEAM
Natalie J. Galant, PhD, Co-Founder and Chief Executive Officer: PhD thesis on antibody for ATTR amyloidosis resulted in a therapeutic licensed by UHN to Prothena Biosciences and eventually acquired by Novo Nordisk for $1.2B (2021); expertise in pre-clinical immunotherapy development and& cardiac amyloidosis.

 Yulong Sun, PhD Co-Founder and Chief Scientific Officer: Broad expertise in protein misfolding diseases; led antibody discovery for 3 preclinical programs, first has already resulted in strategic partnership.

SCIENTIFIC FOUNDER(S)
Natalie J. Galant & Yulong Sun