UBS Private Biotech Summit Highlights Tenvie Therapeutics: First NLRP3 biomarker data in Q4 to support CNS-penetrant obesity/CV thesis

We were pleased to attend the UBS Private Biotech Innovation Summit and appreciated the opportunity to sit down with Mike Yee for a thoughtful conversation.
 
In this fireside chat, Tenvie CEO, President, and Co-Founder Tony Estrada outlined Tenvie’s approach to treating neurological and peripheral diseases, with an emphasis on one of the field's most persistent challenges: getting drugs where they need to go — particularly across the blood-brain barrier.

Read the report from UBS below:

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We hosted Tenvie Therapeutics at our UBS Private Biotech Innovation Summit in NYC and sat down with Co-founder, CEO, and President Tony Estrada, PhD to talk about the company's two clinical assets targeting NLRP3 and SARM1. Tenvie is leveraging more than a decade of experience researching the properties and key transporters in the blood-brain barrier and how to optimize small molecules to safely deliver them to the CNS. The company launched in March 2024 and acquired its assets from leading CNS innovator Denali Therapeutics, where Tenvie CEO Tony Estrada spent 8+ years as Head of Discovery Sciences.

Lead asset TNV262 is a fully CNS-penetrant systemic NLRP3 inhibitor for the treatment of CVD and obesity currently in a Phase I HV and obese patient trial which is scheduled to read out 4-week data by Q4. Tenvie believes that full CNS-penetrance is necessary for weight loss effect: in a mouse model, treatment with a fully CNS-penetrant NLRP3 inhibitor led to gradual, fat-preferred weight loss in obese mice via alleviation of inflammation in the hypothalamus whereas a peripherally-restricted NRLP3 inhibitor did not. The mechanism revolves around resolving neuroinflammation and microglial activation in the hypothalamus which Tenvie believes is disrupting the brain's ability to detect satiety. Previous clinical data from VTYX (acquired by LLY for $1.2B) and others show reduction of peripheral CV markers driven by peripheral NLRP3 inhibition but no weight loss; Tenvie believes you need north of IC90 NLRP3 inhibition in the CNS to drive that weight loss effect and that they have the unique ability to test the NLRP3 thesis in obesity with their fully CNS-penetrant lead candidate TNV262.

Tenvie sees optionality for TNV262 as (1) maintenance therapy and (2) in combination with incretins for overall healthier, more gradual weight loss and CV benefits while addressing the root neuroinflammatory drivers of obesity. Preclinical data are indicative of synergistic weight loss effects of adding NLRP3 on top of semaglutide at therapeutically relevant doses. The added benefit in combination would be the ability to achieve similar weight loss at lower levels of GLP1 which could help mitigate AEs seen with the incretin class.

With their Phase I data Tenvie will aim to (1) recapitulate the CV biomarker data shared by VTYX and others and (2) share data on additional, unique biomarkers to support the cardiometabolic thesis. Tenvie plans to move TNV262 quickly into Phase II studies in CVD and obesity which could initiate by YE and read out in Q4/27 pending first Phase I data by Q4. Note co also has second CNS-penetrant NLRP3 inhibitor set to enter the clinic in August (pot'l here to assess this candidate in neurologic diseases or other indications vs. TNV262) as well as a preclinical candidate that is peripherally restricted.

Tenvie's second asset is a peripherally-restricted SARM1 inhibitor for the treatment of peripheral neuropathies in a Phase I HV trial. Co will have first Phase I safety and PK data in H2/26 and is looking at PK/PD and biomarkers related to pathway modulation and neuroprotection. Co also has a CNS-penetrant SARM1 inhibitor planned to enter the clinic next year to address CNS indications relevant to SARM1. SARM1 is thought to be a root cause/master executer of axonal degeneration and subsequently neuronal death. By inhibiting SARM1, preclinical data demonstrate protection against nerve degeneration in peripheral neuropathies. Potential indications span chemo-induced peripheral neuropathy, DPN, ALS, and a number of other indications. TNV108 is an allosteric inhibitor of SARM1 which locks SARM1 in an inactive state and therefore different from orthosteric inhibitors from LLY (Disarm) and NeuroBio that compete at the active site - Tenvie believes the allosteric approach to be preferable for inhibiting SARM1.

Tenvie also has a number of preclinical programs (TRPML1, TMEM175, etc.) that leverage their expertise in fine-tuning the balance of CNS-penetrance/peripheral restriction for a number of targets and indications.

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Watch the full conversation here.