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21 New “Kids” on the Block: The Most Recent Entrants into the Greater New Haven Biotech Hub

These 21 newly minted biotech spin outs in the last 1–2 years add to an illustrious group of young companies and breakthrough technologies in the Greater New Haven Biotech hub. Most are barely out of stealth mode and are on the hunt for much needed venture financing to transition from the walls of academia to the new world of industry. They are all discovery-stage and pre-clinical companies that are diligently de-risking their drug-like compounds and applications. We’ve split them into 3 groups: (i) Out of stealth mode, (ii) Mostly in stealth mode and (iii) Somewhere between a lab & a venture. Enjoy this read and follow these companies as they innovate for tomorrow’s patients.

Out of Stealth Mode

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Image 1: Word cloud rendering of startups “out of stealth mode.”

1. Athena Therapeutics

More than half a century before metabolic rewiring was included in the landmark Hall Marks of Cancer — The Next Generation Cell paper, Sydney Farber had hypothesized that folate metabolism had a role in leukemia proliferation : a discovery that provided a launchpad for chemotherapies such as methotrexate. Today metabolism continues to be a hot area in the search for new cancer drugs. Athena Therapeutics joins the party with a targeted strategy. Athena’s founders Drs. Ranjit Bindra and Charles Brenner aim to address the rewiring of metabolic pathways that create Nicotinamide Adenine Dinucleotide (NAD), an important co-factor in electron transfer in cells. They believe that they’ve identified the “molecular blueprints” for altered NAD metabolism in cancer. Armed with this knowledge which was published in their Nature Communications paper, Athena intends to create a new class of drugs that selectively target cancer cells with altered NAD metabolism.

2. Halda Therapeutics

Yet another spin-out of Craig Crews’ laboratory at Yale, this research-stage drug discovery company will join its sister Arvinas in a new lab and office space in Science park, New Haven. While much of Halda’s research appears to be in stealth mode, we know one thing for sure, they’ll be looking for a platform on a molecule/ technology with broad applicability across numerous disease states. Co-founded by a seasoned biotech entrepreneur and armed with new venture financing, this is one to watch.

3. EvolveImmune Therapeutics

A frequent standout at Yale’s Life Sciences PitchFest and the Blavatnik Fund’s Innovation showcases, Sidi Chen’s team has joined the red hot field of immuno-oncology and autoimmunity and they are doing it right in their backyard. Leveraging genome editing toolkits and proprietary screening modalities, EvolveImmune aims to discover novel targets across a vast array of immune cells with the goal of developing first-in-class medicines. Having closed on a $35 million Series A round led by Pfizer and Solasta Ventures, Takeda, Elm Street Ventures and Yonjin Venture, the Branford-based biotech has its work cut out under the leadership of Canaan Partners VC Stephen Bloch — a familiar face in the hub.

4. Pangolin Therapeutics

One only needs to look at the pharma landfill of failed Alzheimer’s, Parkinson’s and dementia drugs to realize how challenging the thesis on amyloid states (loosely defined here as aggregation or deposits of beta-sheet proteins in places they shouldn’t be) of disease causing proteins is in this field. Enter Pangolin Therapeutics, from Prof. Miranker’s lab at Yale; they believe clinical trials in amyloidosis have failed as a result of misdirected focus on amyloid states of disease-causing proteins. They developed a proprietary chemistry-driven small-molecule platform, termed Pangomers™, to address this deficiency. Armed with this war chest of validated pangomers, they “seek to address Multiple System Atrophy (MSA), an aggressive, orphan-indicated form of Parkinson’s for which there are no approved therapeutics.”

5. Brainstorm Cancer Therapeutics

Another serial biotech entrepreneur in the hub, Prof. Bindra and his colleague Prof. Saltzman at Yale will join the chorus of biotech companies across the country trying to break past the blood-brain barrier, an Achilles heel in developing treatments for brain cancers and other cancers that eventually metastasize to the brain. BrainStorm Therapeutics is building proprietary nanoparticle formulations and brain tumor biomarkers that may quickly translate to the clinic to address this unmet need.

6. Lambda Vision

Lambda Vision is the second startup in this hub developing medicines for age-related macular degeneration (AMD), but lambda has a different story to tell. It’s founder, Dr. Robert R. Birge, a distinguished professor of chemistry at the University of Connecticut and leader in the field of light-sensitive proteins is developing an artificial protein-based retina which utilizes a light-activated protein to restore functional sight to those who would otherwise be blind due to AMD. Lambda’s solution stands out in a crowded field.

Mostly in Stealth Mode

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Image 2: Word cloud rendering of startups “mostly in stealth mode.”

7. RiboRupt biotech

Ribosome biogenesis is still relatively underappreciated as a target in cancer therapeutics. These complex cellular machines play a key role in making proteins in every living cell. Dysregulation in their function has recently been associated with development of cancers. Most hypotheses hinge on the role of ribosome biogenesis in cell proliferation and cell cycle progression. At RiboRupt Biotech, Dr. Baserga, MD, PhD and her team are interrogating this process to treat cancer. Leveraging a proprietary image-based screening technology, this team has identified several small molecule inhibitors of nucleolar function. They are testing these molecules against a vast array of cancer targets in both cell culture and animal models. It’s early days for RiboRupt, but what they are doing could open a new class of cancer therapeutics.

8. RegenaVision

The search for disease modifying drugs in age related macular degeneration (AMD) is a party that continues to attract many participants ranging from gene therapy companies to those looking to harness innate immunity to address this disease. RegenaVision has developed a high-throughput assays that mimics the effects of oxidative stress in this setting. They have identified three novel chemically distinct drug-like compounds that confer protective properties to retinal cells in the setting of oxidative stress and photo-damage. Mark Fields and his team will hope these compounds are strong candidates for further pre-clinical development.

9. Miso Therapeutics

Like its hub sister Athena, Miso Therapeutics is looking at metabolic targets in cancer. They join a crowded field of US biotech startups and pharma heavy weights working to improve outcomes for Triple Negative Breast Cancer (TNBC). Miso however is not just another metabolism cancer startup. They are going after a novel TNBC target: the mitochondrial isozyme Phosphoenolpyruvate carboxykinase 2 (PCK2). PCK2 currently lacks inhibitors and has limited validated assays to comprehensively interrogate its activity. Miso’s research team will hope that their internally developed assays provided credible hits that will be reproducible in vivo and in humans.

10. Seranova Bio

Rising rock star immunobiologist and protein enginee Aaron Ring has returned to his alma mater, Yale University with a big bang. When he’s not churning out Nature papers, he seems busy building biotech companies. Seranova Bio is the latest spinout from the Ring lab. The company is “discovering drug targets from clinical trials of nature” with a rather unique bedside-to-bench-and-back approach. This biotech plans to screen patients for autoimmune disease and neurodegeneration to identify therapeutic antibodies. In so doing, they hope they can discover antibodies that correlate with favorable clinical responses and translate their findings to the clinic.

11. Eliv5 therapeutics

Eliv5 is shining a new light on fungal infections, an opportunistic and often neglected disease area that can be fatal especially in immunocompromised individuals. According to Eliv5, fungal infections account for 1.5 million deaths worldwide.They’ve completed a screen of ~160,000 small molecules against a group of fungi known as Aspergillus and zeroed in the protein Pantothenate kinase (PanK). PanK is an essential enzyme in all living organisms and plays a key role in several cellular processes including energy production in the krebs cycle. The startup continues to work relentlessly to evaluate the efficacy, pharmacological properties and safety of their most promising compounds from this screen.

12. Targetsite Therapeutics

Commercial and clinical stage biotech companies Alnylam and Arrow Pharmaceuticals garnered attention to RNA interference technology as a potential therapeutic within the biotech community. Jeff Bender at Yale and Vinod Ramgolan bring a fresh set of eyes and a novel approach to RNA-targeting with Targetsite Therapeutics. They’ll take on a rare eye inflammatory disease known as uveitis with their newly developed miRNA Target-based Oligonucleotide candidate. Thus far, they demonstrated that their enhancing miRNA target site blocking oligonucleotide “greatly delays onset and reduces disease severity in the rat uveitis model ” and continue to pursue further target derisking efforts.

13. ADM Therapeutics

Adult onset diabetes (type 2) wherein the body either resists the effects of insulin or doesn’t produce enough insulin to maintain normal glucose levels. Pancreatic cells known as islets modulate this process. When these cells malfunction, the body loses its ability to regulate glucose; predictably current drugs work by helping the body make up for this lost/ diminished ability to regulate glucose. Yale professor Dr. Miranker wants to address the root cause of adult-onset diabetes. With ADM therapeutics, this team will go after insulin’s sister protein, islet amyloid polypeptide (IAPP). According to Dr. Miranker’s group, “when IAPP adopts the wrong shape, it pokes holes in the membranes of islets large enough to kill the insulin-secreting cells.” ADM Therapeutics’ lead compound binds to misfolded IAPP and prevents it from poking holes into the islets.

14. Cytosolix Therapeutics

Targeting the tumor micro-environment as a therapeutic strategy has recently generated a lot of interest among drug developers. The tumor micro-environment exhibits certain distinct properties such as high acidity, unique metabolic states and altered expression of select surface proteins. Former Yale postdoc John Deacon’s startup is leveraging the highly acidic micro-environment of solid tumors with its platform technology Tumor Activated Permeability (TAP) Therapy. Activated by the acidic environment of a tumor, TAP selectively limits the uptake of toxic oncology drugs to solid tumors thereby reducing off-target toxicity. This technology may have broad applicability and could increase the therapeutic index of a vast array of small molecules.

15. Center Pharm

Barbara Ehrlich and her team at Center Pharm have joined the ranks of the Greater New Haven rare disease pioneers Alexion Pharmaceuticals and Rally bio. They will hope the stars align in their pursuit of a treatment for Wolfram Syndrome, a rare inherited condition that presents with childhood-onset insulin-dependent diabetes and gradual vision loss. Based on discoveries in her lab that credentialed neuronal calcium sensor-1 (NCS1) as an important modulator of pathogenesis in Wolfram syndrome, Dr. Ehrlich’s startup is screening to identify new drugs targeting NCS1 stabilization in Wolfram Syndrome patients. They identified a lead molecule that could potentially be a first-in-class drug to slow the progression of this disease.

Somewhere Between a Lab & a Venture

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Image 3: Word cloud rendering of startups “somewhere between a lab and venture.”

16. Alpriant

Alpriant will take on an area that has long been the proverbial junkyard for phase 3 drugs in biopharma — Alzheimer’s disease. Most failed Alzheimer’s drugs have focused on removing amyloid plaques from the brain or slowing the formation of these plaques. Alpriant is taking a different lens to this problem. Rather than focus on removing or slowing down plaque buildup, Prof. Strittmatter is researching a strategy to protect the loss of brain synapses (electrical signals transmitted from one junction to another in brain cells) associated with Alzheimer’s pathology. In the startup’s presentation at the Yale Life Sciences PitchFest, the founders touted their prion protein antagonists ability to “rescue synapses and memory function by interrupting the deleterious signaling triggered by amyloid without removing plaque.”

17. Assyst Therapeutics

Less attention has been paid to nephrology (kidney disease care) in biotech in the past 5–10 years. Much of the fanfare has gone towards oncology, immunology and more recently neurology. Assyst Therapeutics is shining a light on the unmet need in Autosomal Dominant Polycystic Kidney Disease, the most common single gene cause of kidney failure. To address this need, the startup is targeting regulatory proteins (Ire/Xbp1) that are associated with cellular responses to stress and kidney inflammation.

18. Apira

Joseph N. Contessa, Professor and Vice Chair, Therapeutic Radiology at Yale Cancer Center will keep his sights on improving standard of care for glioblastoma (an incurable type of brain cancer) by extending recently published work from his team with his latest endeavor, Apira biotech. Receptor tyrosine kinases (RTKs) are regulatory transmembrane proteins that play a key role in how cells grow and survive. When their ability to tightly control this function is rewired by a mutation, one can develop glioblastoma. Some current therapies focus on targeting these rewired RTKs, however, cancer cells quickly figure out a way to bypass the RTK pathway thus resulting in resistance to therapy. Prof. Contessa’s team has discovered a way to re-sensitize these resistant cells to therapy by inhibiting a signaling sugar moiety that’s critical to how RTKs are activated . This represents a novel approach in the fight against this fatal disease. Fresh off a high potential impact award from Yale’s premier early stage biotech innovation showcase, this team is looking to advance a clinical candidate for testing in glioblastoma patients.

19. Rarebase Therapeutics

Yale epigeneticist and stem cell biologist Andrew Xiao’s startup has its story in the name — Rarebase Therapeutics. Nothing creative in the name, but a series of groundbreaking stories that have so far graced the pages of biomedicine’s most prestigious peer-reviewed journals. Xiao’s research has revealed that an obscure base in the DNA (so-called the 6th base) is partly responsible for how cancers acquire resistance to drugs. Suffice it to say, they’ve put their best talents towards identifying chemical inhibitors to block the synthesis of this rare base. This is another one to watch, if not for the translational possibilities, then definitely for the beauty of its science.

20. Virtus Therapeutics

Virtus joins the hunt for disease modifying therapies for neurodegenerative disorders — an area filled with so much biotech activity but little real progress to show for it the clinic. They are going after a rather specific slice of the pie — Pantothenate Kinase-Associated Neurodegeneration ; a disabling genetic disorder that manifests with young on-set of Parkinsonism. Choukri Ben-Mamoun, Ph.D. and the Virtus team hope that by activating the PanK3 enzyme, they can address some aspects of this disease. It’s still early days for this group as they await the results of their structural and pharmacological characterization of PanK inhibitors in animal models.

21. Pearl Bio

Nature is the best engineer but the occasional mistakes it makes can be fatal and notoriously difficult to fix. Our biology is constrained to about 20 natural amino acids — the building blocks for proteins that make up nearly everything that sustains human life. Engineering these building blocks to improve desirable features of protein-based drugs (such as longer half-life and better target engagement) is incredibly challenging. By founding Pearl Bio, Yale’s Farren Isaacs is reframing this challenge and pioneering design and production of next generation biologics and biomaterials that can be precisely adjusted by biological engineers. Pearl Bio will apply this to select indications in oncology, immunology and rare disease.

Closing Thoughts

Translation of many of these amazing scientific efforts from bench to bedside is a much longer marathon — one fraught with limitless risk, a low success probability and often lengthy detours. If you hit 100 quality shots on goal, soon or later you’ll hit a game winner. If you’ve been following our blogs to this point, one thing should be clear by now: the Greater New Haven Biotech hub is leaving no stone unturned in this quest to claim its throne as the newest member of the biotech heavy hitters club.

Authored by Samuel Kitara & Jun Chen

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