–Series B co-led by MRL Ventures Fund (MRLV) and Bayland Capital, with participation from Johnson & Johnson Innovation – JJDC Inc., LAV Fund, BioTrack Capital, and Sherpa Health Partners–

–First patient dosed in Phase 1 clinical study of lead candidate PT0253, a potent, selective KRAS G12D degrader–

BURLINGTON, Mass., May 7, 2025 – PAQ Therapeutics, a biotechnology company developing best- and first-in-class KRAS degraders for patients with lethal cancers lacking effective treatment options, today announced the completion of its $39 million Series B funding. The Series B round was co-led by Bayland Capital and MRL Ventures Fund (MRLV), with participation from Johnson & Johnson Innovation – JJDC, Inc. (JJDC), LAV Fund, BioTrack Capital, and existing investor Sherpa Health Partners.

The capital raised will fund PAQ’s next stage of clinical development for the company’s lead asset PT0253, a potent and selective degrader of KRAS G12D, a known driver for a range of solid tumors. PT0253 has demonstrated best-in-class potential based on preclinical comparison to existing agents currently in clinical development targeting the same KRAS mutant. In Q1 2025, the first patient was dosed in Phase 1 study to assess its safety and tolerability.

“The successful completion of our Series B funding and rapid enrollment of our Phase 1 trial in the US for PT0253 mark significant steps forward in our clinical development efforts,” said Nan Ji, PhD, PAQ’s co-founder, President, and CEO. “The strong support from our investors validates the potential of our innovative approach. We now turn our focus to executing a robust clinical development plan while continuing to develop a differentiated pipeline of KRAS degraders.”

The funds will also support the advancement of the company’s second asset through IND-enabling studies.

“PAQ represents a compelling opportunity to develop transformative therapies for oncology populations with high unmet need,” said Olga Danilchanka, Partner, MRLV, the therapeutics-focused corporate venture arm of Merck & Co. “Their innovative efforts advancing the targeted protein degradation modality aligns with our commitment to backing scientifically rigorous teams that tackle pressing medical challenges. We’re confident in PAQ’s ability to unlock the full potential of KRAS degraders and are proud to support their journey toward achieving clinical impact.”

“The team at PAQ is at the forefront of an innovative approach to treat some of the most underserved patient populations in oncology,” said Yuexing Su, Founding Partner, Bayland Capital. “We were attracted to PAQ based on its scientific approach, preclinical data, and experienced leadership team. We believe there is tremendous potential for KRAS degraders and are excited to be part of PAQ’s next stage of growth.”

PAQ Therapeutics was founded in 2020 and completed a $30M Series A financing in 2021. Over the last three years, the PAQ team gained proprietary understanding of KRAS biology, which guided medicinal chemistry to identify KRAS degraders. These programs have the potential to address key limitations of clinical-stage KRAS inhibitors, offering more effective and durable treatments.

About PAQ Therapeutics

PAQ Therapeutics is a clinical-stage biotechnology company developing best- and first-in-class KRAS degraders for lethal cancers lacking effective treatment options.

–Expansion of leadership to facilitate robust clinical development strategy, progress company pipeline of potent and selective KRAS degraders–

BURLINGTON, Mass., May 7, 2025 – PAQ Therapeutics, a biotechnology company developing best- and first-in-class KRAS degraders for lethal cancers lacking effective treatment options, today announced that Andrew Krivoshik, MD, PhD, has joined the company as Chief Medical Officer (CMO). He will play a critical role during a key year for the company as PAQ advances its lead asset PT0253, a selective KRAS G12D degrader progressing in the clinic, and a second asset through IND-enabling studies.

“We are excited to welcome Dr Andrew Krivoshik to the team, as he brings a wealth of experience in delivering much-needed oncology medicines to patients, in addition to a strong understanding of the unmet need that currently exists in KRAS-driven cancers,” said Nan Ji, PhD, Co-Founder, President and CEO, PAQ Therapeutics. “With Andrew’s strategic guidance, and advisory board additions of industry and academic experts Drs Eric Rubin and Piro Lito, we strongly believe that we have the right team and a clear path forward to advance a compelling pipeline of KRAS degraders.”

Dr Krivoshik brings extensive development experience across a range of therapeutic modalities spanning small molecules, antibodies, protein degraders, gene therapies, oncolytic viruses, and others. He has had a distinguished career in the development of new medicines for patients marked by the successful leadership of multidisciplinary teams, which played a significant role in the approval of multiple oncology products – XTANDI^®, XOSPATA^®, PADCEV^®, and VYLOY^®.

“I am thrilled to join the company as PAQ develops the next wave of KRAS degraders,” said Andrew Krivoshik, CMO, PAQ Therapeutics. “PAQ is uniquely positioned to potentially translate an innovative approach into meaningful therapies for patients with a range of cancers driven by KRAS mutations. I look forward to working with the team and clinical investigators to advance our pipeline, shape our clinical strategy, and ultimately, bring transformative treatment options to those who need them the most.”

Prior to joining PAQ Therapeutics, Dr Krivoshik served as the Chief Medical Officer at Frontier Medicines. He also held several senior leadership positions at Astellas Pharma Global Development, where as President and Head of Development, he was responsible for managing global clinical development activities and functions, as well as the design and implementation of clinical studies. Dr Krivoshik earned his MD and PhD from the University of Illinois at Urbana-Champaign and a BSE from Princeton University.

PAQ also announced the addition of two new advisors to help guide the company as additional pipeline assets advance to the clinic:

• Eric H. Rubin, MD, joins as the Chair of the Clinical Advisory Board. Dr Rubin has focused on cancer drug development for more than 30 years. Prior to retiring in late 2023, he led the oncology early clinical development team at Merck Research Laboratories. Dr Rubin was instrumental in the initial development of pembrolizumab – the first anti-PD-1 approved in the US.

• Piro Lito, MD, PhD, joins as a Scientific Advisor. Dr Lito is an expert in understanding how RAS mutations drive tumor growth and has developed several RAS-directed therapies.  

“PAQ is at the forefront of pioneering efforts geared to treat some of the most underserved patient populations in oncology,” said Dr Rubin. “Degraders offer a compelling means to target KRAS-containing tumors, and I look forward to working with the team at this important stage in development.”

“I am thrilled to be a part of PAQ’s growth during such a pivotal moment in the company’s evolution,” said Dr Lito, Member and Professor at Memorial Sloan Kettering Cancer Center. “Targeting KRAS through targeted protein degradation holds tremendous promise in addressing the challenges associated with targeting KRAS-driven cancers. I am excited to work alongside such a talented scientific team to help bring forward novel therapies that can improve patient outcomes.”

About PAQ Therapeutics

PAQ Therapeutics is a clinical-stage biotechnology company developing best- and first-in-class KRAS degraders for lethal cancers lacking effective treatment options.

CAMBRIDGE, Mass., September 9, 2021/PRNewswire/ — PAQ Therapeutics (“PAQ”), a biotechnology company harnessing the power of autophagy to restore health and cure disease, and Insilico Medicine (“Insilico”), an end-to-end artificial intelligence (AI)-driven drug discovery company, today announced that the companies have entered into a collaboration agreement to develop small molecule therapies designed to hijack the autophagy pathway to address novel disease targets.

Under the terms of the agreement, both parties will leverage Insilico’s small molecule compound generation platform Chemistry42 and other AI-powered drug discovery technologies in combination with PAQ’s autophagosome-tethering compound (ATTEC) technology platform to discover novel small molecules with the potential to catalyze and selectively enhance the degradation of disease-causing entities through autophagy.

Autophagy is the natural cellular degradation mechanism that removes unnecessary or dysfunctional components through a lysosome-dependent mechanism. With its powerful ATTEC technology platform, PAQ expands the therapeutic potential of autophagy to target not only disease-causing proteins, but also lipids, pathogens, and other substrates with the goal of restoring health. Insilico’s AI-powered drug discovery platforms utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques to speed the generation of new molecular structures with specific properties, improving the efficiency and success of drug discovery.

“PAQ’s autophagy-dependent approach supports a pivotal moment in the evolution of drug discovery and design by expanding the ability to target the disease-causing substrates underlying diseases with limited or no treatment options,” said Feng Ren, Ph.D., Chief Scientific Officer and Head of Drug R&D at Insilico. “Insilico is pleased to partner with PAQ Therapeutics to leverage our AI-driven drug discovery platforms in advancing drug R&D of ATTECs to address unmet medical needs.”

“As part of PAQ’s ongoing efforts to therapeutically harness autophagy-dependent degradation, one key next step is to integrate cutting-edge technologies like AI that support our overall hit-finding and drug discovery strategy,” said Nan Ji, Ph.D., Co-founder, President and CEO, PAQ Therapeutics. “We are excited to leverage Insilico’s deep expertise and proven track record in AI-driven drug discovery during a pivotal time in our company’s growth and progress.”

About Insilico Medicine

Insilico Medicine, an end-to-end artificial intelligence-driven drug discovery company, is developing artificial intelligence platforms. These platforms use deep generative models, reinforcement learning, transformers, and other modern machine learning techniques for novel target discovery and the generation of novel molecular structures with desired properties. Insilico Medicine is developing breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, infectious diseases, autoimmune diseases, and age-related diseases. For more information, visit www.insilico.com.

About PAQ Therapeutics

PAQ Therapeutics is a biotechnology company pioneering a new approach to restoring heath and curing disease through autophagy, the body’s most versatile mechanism for natural cellular degradation. With our ATTEC (autophagosome-tethering compound) technology, we are developing a novel class of small molecule degraders capable of binding a diverse array of substrates to the autophagy pathway. PAQ’s research advances are driving an important new class of degradation therapies with the potential to fundamentally transform drug discovery and development and target a range of substrates including proteins, aggregates, lipids, organelles, and pathogens. For more information, visit www.paqtx.com.

Advancing beyond protein targeting to develop novel autophagosome-tethering compounds (ATTECs) to catalyze and selectively enhance the degradation of disease-causing entities through autophagy

Initial focus on a genetic neurodegenerative disorder with potential to treat a range of diseases without current therapeutic options

CAMBRIDGE, Mass., July 15, 2021 – PAQ Therapeutics, a biotechnology company pioneering a new approach to restoring heath and curing disease through autophagy, today announced the completion of its $30 million Series A financing. PAQ’s approach and technology expands the therapeutic potential of autophagy – the body’s most versatile mechanism for natural cellular degradation – to target not only disease-causing proteins but lipids, pathogens and other substrates with the goal of restoring health. Sherpa Healthcare Partners led the Series A financing with participation from Huagai Capital, MSA Capital, and MRL Ventures Fund, joined by seed investors, Nest.Bio Ventures and Matrix Partners China.

PAQ’s novel autophagosome-tethering compounds (ATTECs) are small molecules with the potential to selectively catalyze autophagy-dependent degradation of a wide range of disease-causing substrates, including proteins and non-protein substrates, such as aggregates, mitochondria, lipids and pathogens. PAQ is initially focused on a genetic neurodegenerative disorder, with the potential to expand the breakthrough ATTEC platform to target disease-causing protein and non-protein targets for a range of diseases with limited treatment options. The Series A financing will allow the company to advance its ATTEC platform and progress its pipeline programs.

“PAQ’s team of global experts are working to hijack the powerful autophagy pathway to directly target and eliminate disease-causing substrates from the body,” said Nan Ji, Ph.D., PAQ’s Co-founder, President and CEO. “PAQ’s ATTEC technology provides a complementary and differentiated platform to targeted protein degradation (TPD), which works through the ubiquitin-proteosome (UPS) pathway. Our autophagy-dependent approach further supports a pivotal moment in the evolution of drug discovery and design by expanding our ability to target the disease-causing substrates beyond proteins underlying diseases with limited or no treatment options.”

Based in Cambridge, Massachusetts, the global PAQ team collectively brings decades of drug discovery experience and significant expertise in autophagy research. Joining Dr. Ji as co-founders are Huaixiang Hao, PhD, Head of Biology and Professor Boxun Lu of Fudan University in Shanghai, China. PAQ’s scientific advisors are distinguished research leaders in autophagy, neuroscience, drug discovery including:

• David Rubinsztein, PhD, Professor of Molecular Neurogenetics and a UK Dementia Research Institute Group Leader, University of Cambridge
• Jared Rutter, PhD, Distinguished Professor of Biochemistry, Dee Glen and Ida Smith Endowed Chair for Cancer Research, University of Utah
• Jin-Quan Yu, PhD, Frank and Bertha Hupp Professor of Chemistry, The Scripps Research Institute
  

“Dr. Nan Ji has assembled a strong team of leading autophagy researchers and scientific advisors focused on advancing the ATTEC platform,” said Cheng Xing, Managing Partner of Sherpa Healthcare Partners. “We see tremendous potential for autophagy-dependent degradation to achieve major therapeutic innovations leveraging the flexibility of small molecules to create cures and overcome serious diseases where therapeutic options are limited for patients.”

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About PAQ Therapeutics

PAQ Therapeutics is a biotechnology company pioneering a new approach to restoring heath and curing disease through autophagy, the body’s most versatile mechanism for natural cellular degradation. With our ATTEC (autophagosome-tethering compound) technology, we are developing a novel class of small molecule degraders capable of binding a diverse array of substrates to the autophagy pathway. PAQ’s research advances are driving an important new class of degradation therapies with the potential to fundamentally transform drug discovery and development and target a range of substrates including proteins, aggregates, lipids, organelles and pathogens.

About Sherpa Healthcare Partners

Sherpa Healthcare Partners (“Sherpa”) is a healthcare-focused venture capital fund founded in 2018 by an experienced team of healthcare investment professionals. The team has made over 50 investments in leading companies in key areas such as Pharma, GeneTech, MedTech and Medical services. Sherpa is committed to investing in impactful technologies and supporting the success of aspiring entrepreneurs.

About Nest.Bio Ventures

Nest.Bio is a venture creation and venture capital firm focused on leveraging technological breakthroughs to develop, fund, and commercialize next-generation therapeutics globally. As an active partner in the transformation of revolutionary science into leading healthcare companies, Nest.Bio brings deep scientific, financial, operational and transactional expertise to create an ideal international ecosystem for entrepreneurs, scientists and seasoned executives.

About Matrix Partners China

Matrix Partners China is an early-stage venture capital firm in China founded in 2008. With biopharmaceutical and medical technologies as one of its most dedicated areas, Matrix Partners China is committed to building long-term relationships with driven entrepreneurs and helping them build industry-leading companies.

Media Contact:

Jennifer Arcure
Verge Scientific Communications
jarcure@vergescientific.com

Many diseases are caused by aberrant accumulation of certain proteins that are misfolded and cytotoxic, and lowering the level of these proteins provides promising treatment strategies for these diseases. We hypothesized that compounds that interact with both the disease-causing protein and the phagophore (autophagosome precursor) protein LC3 may tether the former to phagophores for subsequent autophagic degradation. If true, this autophagosome-tethering compound (ATTEC) concept could be applied to many disease-causing proteins to treat diseases. 

We tested this hypothesis in the scenario of Huntington disease (HD), a neurodegenerative disorder that is caused by the mutant HTT (mHTT) protein with an expanded polyglutamine (polyQ) stretch. In our recent study, we designed a small-molecule microarray-based screening and identified four mHTT-lowering compounds that interact with both mHTT and LC3, but not wild-type (WT) HTT. These compounds target mHTT to phagophores for autophagic degradation without influencing the WT HTT level, and rescue HD-relevant phenotypes in HD cells and in vivo in the fly and mouse HD models.

Interestingly, these compounds interact with the expanded polyQ stretch directly and are able to reduce other disease-causing proteins with expanded polyQ. In summary, our study provides the initial validation of lowering mHTT by ATTEC, providing entry points to new treatment strategies of HD and similar diseases.

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Accumulation of mutant proteins is a major cause of many diseases (collectively called proteopathies), and lowering the level of these proteins can be useful for treatment of these diseases. We hypothesized that compounds that interact with both the autophagosome protein microtubule-associated protein 1A/1B light chain 3 (LC3) and the disease-causing protein may target the latter for autophagic clearance. 

Mutant huntingtin protein (mHTT) contains an expanded polyglutamine (polyQ) tract and causes Huntington’s disease, an incurable neurodegenerative disorder. Here, using small-molecule-microarray-based screening, we identified four compounds that interact with both LC3 and mHTT, but not with the wild-type HTT protein. Some of these compounds targeted mHTT to autophagosomes, reduced mHTT levels in an allele-selective manner, and rescued disease-relevant phenotypes in cells and in vivo in fly and mouse models of Huntington’s disease.

We further show that these compounds interact with the expanded polyQ stretch and could lower the level of mutant ataxin-3 (ATXN3), another disease-causing protein with an expanded polyQ tract. This study presents candidate compounds for lowering mHTT and potentially other disease-causing proteins with polyQ expansions, demonstrating the concept of lowering levels of disease-causing proteins using autophagosome-tethering compounds. 

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