• Montara Therapeutics awarded $3.3 million non-dilutive MJFF grant to develop BrainOnly™ Parkinson’s therapy targeting LRRK2, a genetically validated target with major drug development challenges. 

• New collaboration to use Montara’s BrainOnly platform to create a next-generation brain-selective LRRK2 inhibitor that avoids the irreversible toxicity from unselective peripheral activity. 

Montara Therapeutics, a biotech company pioneering brain-selective therapies for central nervous system (CNS) diseases, today announced it has received a research grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF), in addition to joining MJFF’s LRRK2 Investigative Therapeutics Exchange (LITE) program, which supports the development of new therapies that target LRRK2 while also advancing progress toward new LRRK2-relevant clinical biomarkers.

As part of MJFF’s strategic research agenda to help drug developers validate new findings in Parkinson’s biology and enable novel therapeutic approaches, this latest funding will support Montara’s BrainOnly platform, which seeks to increase the therapeutic index of CNS drugs and enable higher, more effective dosing of CNS-targeted therapies. To achieve this, each BrainOnly product is a two-molecule combination of a brain-penetrant drug with a universal peripheral blocker that is designed to block the brain-penetrant drug’s activity in the periphery, creating brain-specific pharmacology. Montara believes this approach will address major safety and tolerability challenges in the treatment of various neurological diseases, including Parkinson’s disease. 

As part of the collaboration, Montara will develop and design a wholly-owned next-generation BrainOnly LRRK2 inhibitor drug candidate that is paired with Montara’s peripheral blocker to mitigate the adverse effects that can occur when LRRK2 is inhibited in peripheral tissues and organs, such as damage to the lung and kidney. LRRK2 is recognized as the most common cause of inherited Parkinson’s disease. However, no new therapy targeting this protein has succeeded in late-stage clinical trials and reached the market. 

“MJFF’s network and expertise make them a wonderful partner to our mission of developing BrainOnly™ therapies that selectively target the CNS while blocking harmful peripheral effects—in this case, enabling and accelerating the development of new therapies for Parkinson’s,” said Nicholas T. Hertz, Ph.D., Founder and CEO of Montara. “Montara is proud to be counted among the select number of industry collaborators in the LITE program and is looking forward to working with the steering committee—consisting of MJFF staff and key advisors with drug discovery and LRRK2 biology expertise—and receiving vital support toward developing the next generation of Parkinson’s disease treatments.” 

“The LITE initiative seeks to provide opportunities for better understanding Parkinson’s and treating it,” said Dario Alessi, PhD, Director of the MRC Protein Phosphorylation Unit at the University of Dundee and LITE principal investigator. “We welcome Montara to the initiative and are excited to explore how the Company’s BrainOnly platform could unlock the enormous potential of LRRK2-targeted therapies in a way that mitigates adverse effects.” 

“I’m excited to see Montara partnering with The Michael J. Fox Foundation through the LITE program,” said Miratul Muqit, Professor of Experimental Neurology at Dundee and a member of Montara’s Scientific Advisory Board. “This team has an impressive track record in the Parkinson’s space, having advanced a potentially disease-modifying treatment at Mitokinin, and is really well positioned to replicate this success with the BrainOnly™ platform and its promise for LRRK2-targeted therapy.” 

About Montara Therapeutics 

Montara Therapeutics is a preclinical-stage biopharmaceutical company pursuing novel approaches to develop safer and more efficacious treatments for neurological diseases. Montara’s BrainOnly™ platform enables brain-specific pharmacology by leveraging existing and novel chemical warheads, restricting deleterious on-target / off-tissue peripheral activity. BrainOnly holds the potential to drug numerous targets previously considered undruggable, greatly expanding the therapeutic options for patients in need of these therapies. Montara is supported by an outstanding group of investors, including founding investor SV Health Investors’ Dementia Discovery Fund, Two Bear Capital, KdT Ventures, Dolby Family Ventures, and BEVC. For more information, visit montaratx.com.

About the LRRK2 Investigative Therapeutics Exchange (LITE) Program  

The Michael J. Fox Foundation for Parkinson’s Research (MJFF) launched LITE in 2024 to pave the way for new therapeutic approaches for LRRK2, connect companies that are developing LRRK2-targeting therapies with pharma and biotech opinion leaders, and provide preclinical and clinical resources to establish best practices for advancing LRRK2 targeted therapeutics. Mutations in the LRRK2 gene linked to Parkinson’s disease were first discovered in 2004 and are now understood to be the most common cause of inherited PD. Built on MJFF’s dedication to open science, LITE fosters international collaboration across more than 30 academic and clinical centers and more than a dozen companies. The initiative is governed by an active steering committee consisting of MJFF staff and field leaders and is implemented by the University of Dundee in the United Kingdom. The LITE program also will benefit from collaboration with the Aligning Science Across Parkinson’s (ASAP) initiative-supported programs including the Collaborative Research Network (CRN), the Parkinson’s Progression Markers Initiative (PPMI) and the Global Parkinson’s Genetics Program (GP2). Learn more here.

• Syndicate strengthened with new investors and increased commitments from all existing investors. 
• Total Series Seed funding reaches $28M to advance lead epilepsy program to IND, progress neurodegeneration program to development candidate (DC), and accelerate a third undisclosed program. 
• Troy Wilson joins as Chairman of the Board, bringing extensive leadership, operating, and financing experience. 

Montara Therapeutics, a biotech company pioneering brain-selective therapies for CNS diseases, today announced the closing of a $20 million oversubscribed expansion of its Series Seed financing. The round, which brings Montara’s total seed funding to $28 million, includes increased participation from all existing investors, including founding investor SV Health Investors’ Dementia Discovery Fund, Two Bear Capital, Dolby Family Ventures, and KdT Ventures, along with new investments from BEVC and additional investors.  

“As we take this next critical step towards the clinic, we’re thrilled by upsized commitments from our existing investors and welcome the new investors to our syndicate,” said Nicholas T. Hertz, Ph.D., Founder and CEO of Montara. “This funding positions us to deliver on our mission — developing BrainOnly™ therapies, which selectively target the CNS while blocking harmful peripheral effects. It enables us to drive our lead rare epilepsy program to IND within the next 12 months while accelerating a second program for an age-related neurodegenerative disease and a third, undisclosed initiative. The fact that we have been able to rapidly generate in vivo proof of concept and move towards IND enabling studies in just one year underscores the strength of our team and the BrainOnly™ platform.”  

“On behalf of the investor syndicate and the board, we congratulate the Montara team, which has made exceptional progress and achieved all the R&D goals of the original seed round, a culmination of careful planning and outstanding execution during the company’s incubation phase and based on the foundational work from Dr. Kevan Shokat’s lab at UCSF,” commented Dirk Landgraf, Ph.D., Principal at SV and Director. “This team definitively crushed every important milestone with efficiency and integrity. Significantly expanding this funding round, bringing in new committed partners, and strengthening the board of directors, all in what some find a challenging fundraising environment, speak to Montara’s outstanding productivity and the transformative potential of the BrainOnly™ platform for patients,” added J. Seth Strattan, PhD, General Partner at Two Bear Capital and Director.  

In connection with the financing, Troy E. Wilson, Ph.D., J.D., has joined Montara as an Independent Director and Chairman of the Board. Dr. Wilson, a successful serial entrepreneur and current President and CEO of Kura Oncology, has founded and operated multiple successful companies, including Kura, Avidity Biosciences, Wellspring Biosciences, Araxes Pharma, Intellikine, and Ambrx. Dr. Wilson is also participating in the Seed round as an investor.  

“I’m delighted to join Montara at this exciting stage,” said Dr. Wilson. “The BrainOnly™ platform has the potential to revolutionize CNS disease treatment by minimizing or eliminating peripheral side effects and potential toxicities, a major challenge for most CNS-directed therapies. Rather than using co-administered compounds with opposing effects, Montara’s approach employs a universal peripheral blocker, which can be paired with various therapeutic agents. This breakthrough technology has the potential to transform previously undruggable CNS targets into viable therapeutic opportunities and improve the therapeutic index of existing CNS-targeted therapies. I look forward to working with Nicholas, the team, and the board to advance this groundbreaking science and bring transformative treatments to patients.”  

Montara’s BrainOnly™ platform is designed to improve the therapeutic index of CNS drugs and enable higher, more effective dosing of CNS-targeted therapies by blocking peripheral side effects, addressing major safety and tolerability challenges in the treatment of various neurological diseases. The differentiated approach has garnered early interest from multiple potential partners, underscoring the platform’s potential to redefine CNS drug development.

About Montara Therapeutics 

Montara Therapeutics is a preclinical-stage biopharmaceutical company pursuing novel approaches to develop safer and more efficacious treatments for neurological diseases. Montara’s BrainOnly™ platform enables brain-specific pharmacology by leveraging existing and novel chemical warheads, restricting deleterious on-target / off-tissue peripheral activity. BrainOnly holds the potential to drug numerous targets previously considered undruggable greatly expanding the therapeutic options for patients in need of these therapies. Montara is supported by an outstanding group of investors, including founding investor SV Health Investors’ Dementia Discovery Fund, Two Bear Capital, KdT Ventures, Dolby Family Ventures, and BEVC. For more information, visit montaratx.com.

This Endpoints News article explores the creation of Montara Therapeutics by Kevan Shokat and Nicholas Hertz after selling their first neuro startup to AbbVie. Learn more about the founding pair and their BrainOnly™ platform, along with a look at the research, the competitive landscape, and more of the team behind Montara.

Access the full article on the Endpoints News website.

• Many neurological therapies exhibit dose-limiting side effects, and numerous neurological disease targets remain undruggable because of on-target off-tissue peripheral side effects or toxicities. 
• Montara’s BrainOnly™ is a versatile platform designed to prevent peripheral side effects and concentrate neurological drugs’ activity in the brain, enhancing safety, therapeutic index, and efficacy.
• Based on research from the Shokat Lab at UCSF, BrainOnly is broadly applicable with existing or novel small molecule inhibitors and activators targeting neurodegenerative and neurological diseases and brain cancers. 

Montara Therapeutics, Inc. (‘Montara’), a therapeutics company aiming to revolutionize the discovery and development of brain-targeting drugs, announced today the closing of an oversubscribed $8 million seed financing led by SV Health Investors’ Dementia Discovery Fund and co-lead Two Bear Capital. Dolby Family Ventures and KdT Ventures also participated in the round. 

Therapeutics for neurological diseases such as Alzheimer’s disease and other dementias, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and brain cancers must penetrate the blood-brain barrier and be active against the target at the disease site. However, many promising drug candidates fail to advance due to dose-limiting on-target off-tissue peripheral side effects or toxicities that compromise both safety and efficacy. These brain diseases remain among the most significant unmet medical needs with many important targets still considered undruggable.  

To address this challenge, Montara is pioneering BrainOnly, a platform designed to prevent on-target off-tissue peripheral side effects or toxicities of existing and novel drugs to make best-in-class and first-in-class therapies. 

“The unmet needs of patients with neurodegenerative and neurologic diseases and brain cancers are staggering. It’s well understood that uncontrolled peripheral side effects or toxicities associated with brain-targeting drugs are often the barrier to promising treatments. We hope to eliminate this obstacle with our BrainOnly platform, unlocking many previously undruggable neurological targets and delivering a new generation of neuroscience drugs that bring hope to patients and their families,” said Nicholas T. Hertz, Ph.D., Founder and Chief Executive Officer of Montara. “This seed funding provides a critical springboard to advance our internal pipeline toward the clinic and also enable future partnerships.”

How the BrainOnly Platform Works 

The BrainOnly platform enables the development of two-component combination therapies comprising a brain-penetrant target-specific drug and a non-brain penetrant “universal” peripheral blocker. Montara’s novel approach blocks the drug’s activity in the periphery while simultaneously activating and concentrating its activity in the brain. A two-drug combination approach has been clinically validated for Parkinson’s disease by one approved pair, carbidopa and levodopa, with additional programs in development. However, until Montara, there has been no efficient and scalable platform to systematically develop neuroscience drugs that can avoid peripheral side effects or toxicities.  

The BrainOnly platform is based on pioneering research from the Shokat Lab at The University of California, San Francisco (UCSF), and was published in Nature in 2022. The technology is exclusively licensed from UCSF through its Office of Technology Management and Advancement.

Use of Proceeds 

With the seed funding, Montara is advancing its universal peripheral blocker and a neurological disease-targeting drug with proven clinical benefit but severe dose-limiting peripheral side effects. Montara has also initiated chemistry on subsequent programs for Alzheimer’s and Parkinson’s disease. In connection with this financing, Dirk Landgraf, Ph.D., Principal at SV, and J. Seth Strattan, Ph.D., General Partner at Two Bear Capital, have joined Montara’s Board of Directors.  

Dr. Landgraf commented, “We are excited to have worked with the Montara team on the creation of the company as a founding investor. Montara’s approach is differentiated since it activates the drug in the brain instead of using two drugs with counteracting effects on the same target or pathway. Its mission to develop a brain-only pharmacology platform has huge potential to bring safer and more effective therapies to patients suffering from brain disorders like Alzheimer’s disease and other dementias. We look forward to applying SV’s expertise in dementia drug development to support Montara’s ongoing success via a close collaboration.”  

Jenna Aronson, Ph.D., a Principal at Two Bear Capital and board observer, stated, “We are honored to partner with this exceptional team to address a truly fundamental problem in neuroscience drug development. Toxicity from peripheral target engagement has defeated many promising programs, even those with strong genetic validation and good target engagement in the brain. Unlocking these targets will change patients’ lives. We share Nick’s vision for Montara and are dedicated to helping realize the potential of the BrainOnly platform.”

About Montara’s Founders 

Montara was founded in 2023 by Nicholas T. Hertz, Ph.D., and scientific co-founders: UCSF Professor Kevan Shokat, Ph.D., who invented the covalent inhibition approach to target KRAS G12C, a previously undruggable target, and co-founded many successful biotechnology companies; Stanford University Professor Thomas Südhof, M.D., who won the Nobel Prize for his research in vesicle trafficking; and UCSF Professor Martin Kampmann, Ph.D., who has conducted extensive research in aging-associated neurodegenerative diseases. All of the scientific co-founders will serve on Montara’s Scientific Advisory Board. Since the company’s founding, the Dementia Discovery Fund has collaborated with Dr. Hertz on the business plan and the corporate and pipeline strategy. 

Prior to founding Montara, Drs. Hertz and Shokat previously collaborated to found Mitokinin, which advanced a potential first-in-class disease-modifying treatment for Parkinson’s disease. In October 2023, Mitokinin was acquired by AbbVie for $110 million upfront and up to $655 million in total deal value, in addition to tiered royalties.  

About Montara Therapeutics 

Montara Therapeutics is a preclinical-stage biopharmaceutical company pursuing novel approaches to develop safer and more efficacious treatments for neurological diseases. Montara’s BrainOnly platform allows brain-specific pharmacology utilizing existing and novel chemical warheads, restricting deleterious on-target off-tissue peripheral activity. BrainOnly holds the potential to drug numerous targets previously considered undruggable. The company is backed by top-tier investors, including SV Health Investors’ Dementia Discovery Fund, Two Bear Capital, KdT Ventures, and Dolby Family Ventures. For more information, visit montaratx.com.

About The Dementia Discovery Fund 

The Dementia Discovery Fund (DDF), managed by SV Health Investors, is the world’s largest family of specialized venture capital funds that invests exclusively in companies developing or enabling novel therapeutics for dementia. Dementias, including Alzheimer’s Disease, are arguably the largest unmet medical need, with over 55m patients worldwide. With more than $500m raised for this strategy, and offices in London and Boston, DDF capitalizes on global investment opportunities to fulfill its mandate of delivering measurable impact and generating significant financial returns. Utilizing its network of venture partners, entrepreneurs, leading scientists, and strategic partners, DDF invests in and creates new biotech companies and provides thought leadership in the field. DDF is enabled by its limited partners including major pharmaceutical companies (Biogen, Bristol Myers Squibb, Eli Lilly and Co., GSK, Johnson & Johnson, Otsuka (Astex), Pfizer and Takeda), along with AARP, Aegon, Bill Gates, British Patient Capital, NFL Players Association, Quest Diagnostics, UnitedHealth Group, and the non-profits Alzheimer’s Research UK and LifeArc. Learn more at www.ddf.vc.

About Two Bear Capital 

Two Bear Capital was founded in 2019 by Mike Goguen with a mission to empower visionary entrepreneurs to build enduring, impactful companies while benefiting society and delivering for investors. The Two Bear team combines expertise in enterprise technology, cybersecurity, AI, the life sciences, including where these domains intersect, to invest in solutions that make a meaningful difference to markets and to people. Together with the founders in the Two Bear family we believe that the future we want is ours to build. Two Bear Capital has offices in Menlo Park, San Diego, Boston, and New York, with a home base in Whitefish, Montana. For more, visit www.twobearcapital.com.

About Dolby Family Ventures 

Dolby Family Ventures is a venture capital firm investing in early-stage companies and backing visionary entrepreneurs solving the biggest science and engineering challenges across precision neuroscience, life sciences platforms, aerospace, climate, and digital deep tech since 2014. Over this time, Dolby Family Ventures has invested in about 100 companies across these sectors. Learn more at www.dolbyventures.com.

About KdT Ventures 

KdT Ventures is an early-stage venture capital firm focused on the intersection of biology, chemistry, and technology. Founded in 2017, KdT manages $260M+ in committed capital, and has partnered with 55+ science-driven companies and founders across the life science, healthcare, and chemical and materials industries. KdT is often the first check into a company, and supports founders from the earliest stages of company building and commercialization. 

References  

1.  Z. Zhang et al., 2022, Brain-restricted mTOR inhibition with binary pharmacology, Nature, 609(7928):822-828