Press Release

Montréal, QC, Canada (Jan 31, 2024) – 35Pharma, a clinical-stage biopharmaceutical company that designs and develops TGF-beta superfamily therapeutics, today announced it will be participating at the following investor conferences: 

Contact
Julia Schoelermann, VP Corporate Development, 35Pharma
info@35pharma.com

For more information, please visit www.35pharma.com

• Guy Braunstein, MD, PhD is an experienced CMO who previously led global clinical development at multiple Pharma and biotech companies, including as Head of Global Clinical Development at Actelion until its $30 billion acquisition.
• Graham Walmsley, MD, PhD, Managing Member and Co-Founder of Logos Capital, also joins the Company’s board as an observer.
• Strengthening of the board will support clinical development of the Company’s Activin and GDF traps and follows a previously completed Series B financing led by Logos Capital and a Series A financing led by venBio Partners.

Montréal, QC, Canada (Jan 25, 2024) – 35Pharma, a clinical-stage biopharmaceutical company that designs and develops TGF-beta superfamily therapeutics, today announced the appointment of seasoned drug development executive Guy Braunstein, MD, PhD, to its Board of Directors. Graham Walmsley, MD, PhD, also joined the board as an observer. 

“Guy’s successful track record in rapidly progressing numerous agents from early clinical trials to registration is unparalleled,” said Walter Blättler, PhD, 35Pharma’s Chairman. “His extensive drug development leadership expertise will help guide our drug candidates to expeditious clinical validation.”

Dr Braunstein added: “35Pharma is well positioned for near-term clinical validation of their Pulmonary Hypertension, Heart Failure and obesity pipeline. I am extremely enthusiastic about joining the Company at this critical time and supporting the team to rapidly demonstrate the clinical value of these highly differentiated agents with disease modifying potential.”

Dr Braunstein’s appointment follows a previously completed Series B financing led by Logos Capital with participation from Surveyor, Marshall Wace as well as venBio Partners and other existing investors. Dr Walmsley, Managing Member and Co-Founder of Logos Capital, commented: “35Pharma’s unique receptor ectodomain technology can unlock the powerful Activin biology across multiple high-value indications. I look forward to a clinical catalyst-rich 2024 and to working with Guy and the rest of the board to support 35Pharma during this exciting period.”

Richard Gaster, MD, PhD, Managing Partner at venBio, who led the Company’s Series A financing, added: “We take immense pride in our early partnership with 35Pharma, particularly in their groundbreaking ectodomain traps pipeline. The remarkable progress achieved so far fuels our excitement. As we look ahead, we eagerly await clinical proof-of-concept readouts across their extensive development programs, set to begin in 2024.”

Guy Braunstein, MD, PhD, is a trained pulmonologist and was a member of the Executive Committee and Head of Global Clinical Development at Actelion up until its $30 billion acquisition by Janssen. While at Actelion, Dr Braunstein led the development and ultimate approval of several branded drugs for the treatment of Pulmonary Hypertension, establishing Actelion as the PAH market leader. Dr Braunstein’s background also includes the CMO position at Merck Serono, CMO International at Serono, as well as medical executive positions at Astra, Fisons, Rhône-Poulenc Rorer, Glaxo Wellcome, GSK and Chiron. Currently, Dr Braunstein serves as Executive VP and Chief Medical Officer at Idorsia Ltd, where he has been integral to rapidly advancing the company’s broad clinical pipeline, achieving the first registration less than five years after the company’s inception. Over his more than three-decades long industry career, Dr Braunstein led to approval and line extensions of numerous medicines across a diverse group of therapeutic areas.

About 35Pharma 
35Pharma is a clinical-stage biopharmaceutical company specializing in TGF-beta superfamily therapeutics for the treatment of Pulmonary Hypertension, Heart Failure and obesity. 35Pharma leverages its scientific leadership in TGF-beta biology combined with superior protein engineering to discover innovative compounds that selectively and potently neutralize validated pathological TGF-beta ligands while sparing beneficial homeostatic ligands.

Contact
Julia Schoelermann, VP Corporate Development, 35Pharma
info@35pharma.com

For more information, please visit www.35pharma.com

• Phase 1 healthy volunteer study will evaluate HS135 safety, pharmacokinetics and biomarker responses
• HS135 is a highly potent receptor ectodomain trap that neutralizes Activins and GDFs, validated drivers of Pulmonary Hypertension, obesity and cardiometabolic diseases
• Dosing is expected to begin in early 2024

Montréal, QC, Canada (Jan 03, 2024) – 35Pharma, a clinical-stage biopharmaceutical company that designs and develops TGF-beta superfamily therapeutics, today announced it received a No Objection Letter from Health Canada for its Clinical Trial Application to initiate HS135-001, a Phase 1 study of HS135 in healthy volunteers. 

“Overactive Activin and GDF signalling is a genetically and clinically validated driver of Pulmonary Hypertension, obesity and cardiometabolic diseases. 35Pharma developed a portfolio of differentiated agents targeting this rich biology with HS135 being the first to enter clinical testing.” said Ilia Tikhomirov, 35Pharma’s CEO. “HS135 neutralizes Activins and GDFs with best-in-class potency which we expect to translate into superior activity in patients. We will be sharing initial data on safety and biological activity during 2024.”

HS135-001 is a Phase 1, single-center, double-blind, randomized, placebo-controlled clinical trial in healthy postmenopausal women. Key readouts of the study include safety, pharmacokinetics and change in biomarkers related to Activin and GDF biology following subcutaneous administration of HS135. Dosing is expected to begin in early 2024.

About 35Pharma 
35Pharma is a clinical-stage biopharmaceutical company focussed on the design and development of best-in-class transforming growth factor-beta (TGF-beta) superfamily ligand traps for Pulmonary Hypertension, obesity and cardiometabolic diseases. 35Pharma leverages its scientific leadership in TGF-beta biology combined with superior protein engineering to discover innovative compounds that selectively and potently neutralize validated pathological TGF-beta ligands while sparing beneficial homeostatic ligands. 

Contact
Julia Schoelermann, VP Corporate Development, 35Pharma
info@35pharma.com

For more information, please visit www.35pharma.com

• HS235 is a first-in-class Activin and GDF ligand trap that leads to fat-selective weight loss in vivo
• HS235 in combination with incretins further deepens fat loss while maintaining lean mass

Montreal, QC, Canada (Oct. 16, 2023) – 35Pharma, a biopharmaceutical company that designs and develops TGF-beta superfamily therapeutics to treat cardiopulmonary and cardiometabolic diseases, today presented results from its HS235 program at Obesity Week in Dallas, TX, USA (Oct. 14 – 17, 2023).

HS235 is a potent and multi-specific trap targeting Activin and GDF ligands, including myostatin, which are validated drivers of cardiometabolic disease. Simultaneous neutralization of these ligands by HS235 prevents Activins and GDFs functionally compensating for each other.  In addition, HS235’s ligand trapping mechanism preserves beneficial Activin receptor mediated homeostatic signaling.

The data reported at Obesity Week today demonstrates that HS235 exhibits best-in-class potency against cardiometabolic Activin and GDF ligands while sparing beneficial BMP ligands. In mice, HS235 treatment leads to fat-selective weight loss which is particularly pronounced in combination with incretins.

Highlights of the data presented include:

• HS235 with caloric restriction led to weight loss exclusively due to loss of fat in a diet induced obesity (DiO) mouse model 
• HS235 + tirzepatide demonstrated additive fat loss in a DiO model:
  • Mice treated with tirzepatide alone lost 46% of their fat mass
  • HS235 + tirzepatide led to 64% reduction in fat mass
• HS235 completely rescued lean mass lost by tirzepatide
• All weight loss of the HS235 + tirzepatide combination was exclusively due to loss of fat 

Maureen O’Connor, CSO of 35Pharma commented: “The data presented today establishes that HS235 has a unique mechanism of action that results in weight loss exclusively due to loss of fat. Importantly, HS235’s mechanism is orthogonal to incretins and offsets the undesirable lean mass loss experienced with this class of drugs.”

About 35Pharma
35Pharma is a biopharmaceutical company focussed on the design and development of best-in-class transforming growth factor-beta (TGF-beta) superfamily ligand traps for cardiopulmonary and cardiometabolic diseases. 35Pharma leverages its scientific leadership in TGF-beta biology combined with superior protein engineering to discover innovative compounds that selectively and potently neutralize validated pathological TGF-beta ligands while sparing beneficial homeostatic ligands.

Within cardiopulmonary disease, the company is focussed on developing HS135, a highly potent and selective Activin and GDF trap in Pulmonary Hypertension (PH). Imbalanced Activin and BMP signalling is genetically and clinically validated to drive PH.

Within cardiometabolic disease, 35Pharma is developing HS235, which is a multi-specific trap designed to achieve maximum neutralization of Activins & GDFs, including myostatin, while sparing muscle-anabolic TGF-beta ligands. Concomitant blockade of muscle catabolic Activins and GDFs is genetically and clinically validated to improve body composition and glucose homeostasis. 

Contact
Julia Schoelermann, VP Corporate Development, 35Pharma
info@35pharma.com

For more information, please visit www.35pharma.com

• HS135 demonstrates enhanced in vivo PAH efficacy across lung and heart readouts, including normalization of RV gene expression
• HS135 entirely normalizes expression of heart failure markers in LV and reverses lung congestion and pulmonary vessel remodeling in a Left Heart Failure model

Montreal, Canada (Mar. 5, 2023) – 35Pharma, a biopharmaceutical company that designs and develops biologics for cardiopulmonary and metabolic diseases, today reported preclinical results from its HS135 program in an oral presentation at the American College of Cardiology’s 72nd Annual Scientific Session together with the World Congress of Cardiology (ACC.23/WCC) in New Orleans, LA, USA (Mar. 4 – 6, 2023).

TGF-beta superfamily growth factors Activins and GDFs are validated targets driving the pathophysiology of cardiopulmonary diseases. While previous agents directed against these growth factors have shown considerable therapeutic promise in clinical trials, full pathway inhibition remains a challenge. 

HS135, an engineered Activin receptor II ectodomain (ActRII) -based Fc-fusion protein, has been rationally designed for best-in-class Activin and GDF in vivo target engagement and optimal pathway rebalancing. 

The data reported at ACC.23/WCC today demonstrate HS135’s enhanced and differentiated efficacy in pre-clinical models of Pulmonary Hypertension and Left Heart Failure.

Highlights of the data presented include:

• HS135’s best-in-class potency profile translates into full in vivo target engagement in mice as measured by complete suppression of FSH, a biomarker of Activin and GDF inhibition
• HS135 showed higher and differentiated efficacy in a rat Monocrotaline model of Pulmonary Arterial Hypertension (PAH):
  • HS135 dose-dependently improved pulmonary arterial pressure as well as pulmonary vessel muscularization and normalized inflammatory gene expression in the lung
  • HS135 dose-dependently returned parameters of right heart failure to baseline and normalized gene expression in the right ventricle to levels comparable to normal, naive animals
• HS135 showed enhanced and differentiated efficacy in a mouse therapeutic transverse aortic constriction (TAC) model of Left Heart Disease:
  • HS135 dose-dependently reduced left-ventricular expression of markers or heart failure and fibrosis to baseline
  • HS135 dose-dependently reversed lung congestion and pulmonary vessel remodeling to baseline levels
• In each case, HS135 achieved a deeper and differentiated response compared to dose-matched ActRIIA-Fc

Maureen O’Connor, Chief Scientific Officer and President of 35Pharma commented: “The data presented today at ACC.23/WCC demonstrate that HS135’s best-in-class profile translates into deeper responses in vivo. These results illustrate the potential of HS135 as a differentiated disease modifying approach to address Pulmonary Hypertension and Heart Failure.”

About 35Pharma and HS135
35Pharma is a biopharmaceutical company that designs and develops best-in-class transforming growth factor-beta (TGF-beta) superfamily ligand traps for cardiopulmonary and metabolic diseases. HS135 is a multi-specific receptor ectodomain ligand trap designed to achieve maximum neutralization of Activins & GDFs, clinically validated drivers of cardiopulmonary and metabolic disease. HS135 is undergoing IND enabling development.

Contact
Julia Schoelermann, VP Business Development, 35Pharma
info@35pharma.com

For more information, please visit www.35pharma.com

• HS135 is an ActR-based trap targeting activin A and GDF-8 with best-in-class in vivo target engagement
• HS135 demonstrates superior efficacy in a model of Pulmonary Hypertension as well as positive impact on body composition and metabolism

Montreal, QC, Canada (Nov. 7, 2022) – 35Pharma, a biopharmaceutical company that designs and develops innovative biologics for cardiopulmonary diseases, today presented new preclinical results from its HS135 program at the 2022 American Heart Association Scientific Sessions (“AHA 2022”) in Chicago, IL, USA (Nov. 5 – 7, 2022).

TGF-beta superfamily growth factors activin A and GDF-8 are validated targets driving the pathophysiology of cardiopulmonary diseases. While previous ligand traps directed against these growth factors have shown great therapeutic promise in clinical trials, full pathway inhibition remains a challenge.

HS135 is an engineered activin receptor IIB ectodomain (ActRIIB) -based Fc-fusion protein. HS135 is rationally designed to achieve full pathway inhibition and optimal rebalancing of pathological and homeostatic TGF-beta superfamily ligands.

The data reported at AHA today demonstrate that HS135’s best-in-class target engagement translates into superior in vivo efficacy in Pulmonary Hypertension (PH), and, uniquely amongst tested ActR benchmarks, improved metabolism.

Highlights of the data presented include:

• HS135, but not ActRIIA-Fc, is capable of achieving full in vivo target engagement as measured by inhibition of FSH in mice, a marker of Activin and GDF pathway blockade
• HS135, but not ActRIIA-Fc, positively impacts body composition and muscle metabolism
• In a rat monocrotaline (MCT) model of PH, HS135 demonstrated superior efficacy compared to ActRIIA-Fc including the following read-outs:
  • HS135 exhibited more profound reverse remodelling of pulmonary vasculature
  • HS135 restored several parameters of right ventricle (RV) function to baseline
  • HS135 returned RV gene expression profile to a near normal state

Maureen O’Connor, CSO of 35Pharma commented: “The data presented today indicate that HS135’s best-in-class target engagement translates into significantly increased and differentiated efficacy. I am particularly encouraged by HS135’s pronounced effect on protecting the right ventricle and improving metabolic dysfunction, both of which are established risk factors in cardiopulmonary disease.”

About 35Pharma and HS135
35Pharma is a biopharmaceutical company that designs and develops best-in-class transforming growth factor-beta (TGF-beta) superfamily ligand traps for cardio-pulmonary and -metabolic diseases. HS135 is a multi-specific receptor ectodomain ligand trap designed to achieve maximum neutralization of Activins & GDFs, clinically validated drivers of cardio-pulmonary and -metabolic disease. HS135 is undergoing IND enabling development.

Contact
Julia Schoelermann, VP Business Development, 35Pharma
info@35pharma.com

For more information, please visit www.35pharma.com