Another star is born: Vega Therapeutics targets protein S for bleeding disorders
Another star is born: Vega Therapeutics targets protein S for bleeding disorders
December 6, 2022
December 6, 2022
By: Cormac Sheridan, Bioworld
By: Cormac Sheridan, Bioworld
Vega Therapeutics Inc. emerged from stealth in advance of a podium presentation at this year’s American Society of Hematology (ASH) meeting in New Orleans. The company, a spin-out from Star Therapeutics Inc., will disclose preclinical data on its lead drug candidate VGA-039, a first-in-class antibody in development for von Willebrand disease, a bleeding disorder caused by a lack of von Willebrand factor, a protein required for clot formation. It plans to move the drug candidate into a phase I trial in healthy volunteers early next year, having recently secured approval for the study from Austria’s regulator.
Star Therapeutics, of South San Francisco, is building a portfolio of firms focused on rare disease, and Vega, also of South San Francisco, is the second venture it has unveiled this year. Electra Therapeutics Inc. launched in February with an $84 million series B round and revealed plans to develop a pipeline of antibodies targeting the signal regulatory protein (SIRP) family of cell-surface receptors for immunological diseases and cancer.
Vega has so far raised $40 million from Star Therapeutics and its investors, who include Westlake Village Biopartners, Orbimed, Redmile Group, RA Capital, Cowen Healthcare Investments, Cormorant Asset Management and New Leaf Venture Partners.
Securing a podium slot at ASH for a preclinical data presentation “was a pleasant surprise,” Adam Rosenthal, who is CEO of both Vega and Star, told BioWorld. The antibody’s novel mechanism and potentially broad applicability have elicited interest. VGA-039 targets protein S, a potassium-dependent glycoprotein, synthesized in the liver, which has an inhibitory effect on clot formation. It acts as a co-factor for two anti-coagulatory proteins: protein C, a serine protease which, when activated, degrades the active forms of coagulation factors V and VIII, and tissue factor pathway inhibitor alpha, which inhibits the tissue factor-factor VIIa (TF-fVIIa) catalytic complex and prothrombinase.
It appears to play a controlling role, by rebalancing disruptions in coagulation that are associated with a variety of different causes. “We believe it can be a universal hemostatic therapy across a wide range of bleeding disorders,” Rosenthal said. The ASH presentation will include data on the ability of VGA-039 to restore thrombin generation and clot formation in a series of assays that mimicked the absence of von Willebrand factor, FVII, FVIII, FIX and FXIII. The antibody also increased fibrin deposition in the presence of a neutralizing anti-FVIII antibody.
A 2018 study, led by Anne Angelillo-Scherrer, at Bern University Hospital, in Switzerland, previously showed that targeting protein S in murine models of hemophilia improved coagulation. “That was part of the validation for going after this,” Rosenthal said.
Von Willebrand disease, which is usually inherited in an autosomal dominant fashion, is characterized by lifelong bleeding episodes and accompanying joint damage, although the severity of the condition can vary considerably. Unlike X-linked bleeding disorders such as hemophilia A and hemophilia B, it affects males and females with equal prevalence, but women can experience more severe symptoms, particularly during menstruation. They are also at a higher risk of mortality during childbirth.
Recombinant factor replacement therapy is available either for on-demand treatment or for reducing bleeding severity during surgery. Severe patients may require regular prophylaxis, which entails a twice-weekly infusion. In developing VGA-039, Vega has taken inspiration from Hemlibra (emicizumab), the bispecific antibody developed for hemophilia A by the Genentech arm of Basel, Switzerland-based Roche Holding AG and its majority-owned Tokyo-based subsidiary, Chugai Pharmaceutical Co. Ltd. Now a multibillion-dollar blockbuster, the product has allowed patients to eliminate or reduce the need for regular, time-consuming intravenous FVIII infusions. It can be self-administered by subcutaneous injection – dose schedules range from once weekly to once monthly. “It’s been transformational in people’s lives,” Rosenthal said.
Vega has similar ambitions for VGA-039, and it has already obtained supporting pharmacokinetic and pharmacodynamic data in nonhuman primates. The phase I study will enable it to track its activity even in healthy volunteers, before it can be tested in patients. “What’s nice is there are great biomarkers,” Rosenthal said. Thrombin generation and accumulation of d-dimer – a breakdown product arising from dissolved clots – can be readily measured.
The Vega team already has clocked up extensive experience in building a successful rare blood disorder program at True North Therapeutics. Early clinical data in cold agglutinin disease for an antibody targeting complement component 1s (C1s) prompted a buyout offer in 2017 of up to $825 million from Bioverativ, which Paris-based Sanofi SA then acquired for $11.6 billion. The True North antibody, now known as Enjaymo (sutimlimab), gained U.S. FDA approval earlier this year.
Vega, Rosenthal said, is “open-minded” about the commercial strategy for VGA-039. Its forthcoming debut at ASH has already prompted inward interest from a number of pharmaceutical firms. But the company is also positioning the program for the long term. “We’re developing this drug to take it all the way.”
Vega Therapeutics Inc. emerged from stealth in advance of a podium presentation at this year’s American Society of Hematology (ASH) meeting in New Orleans. The company, a spin-out from Star Therapeutics Inc., will disclose preclinical data on its lead drug candidate VGA-039, a first-in-class antibody in development for von Willebrand disease, a bleeding disorder caused by a lack of von Willebrand factor, a protein required for clot formation. It plans to move the drug candidate into a phase I trial in healthy volunteers early next year, having recently secured approval for the study from Austria’s regulator.
Star Therapeutics, of South San Francisco, is building a portfolio of firms focused on rare disease, and Vega, also of South San Francisco, is the second venture it has unveiled this year. Electra Therapeutics Inc. launched in February with an $84 million series B round and revealed plans to develop a pipeline of antibodies targeting the signal regulatory protein (SIRP) family of cell-surface receptors for immunological diseases and cancer.
Vega has so far raised $40 million from Star Therapeutics and its investors, who include Westlake Village Biopartners, Orbimed, Redmile Group, RA Capital, Cowen Healthcare Investments, Cormorant Asset Management and New Leaf Venture Partners.
Securing a podium slot at ASH for a preclinical data presentation “was a pleasant surprise,” Adam Rosenthal, who is CEO of both Vega and Star, told BioWorld. The antibody’s novel mechanism and potentially broad applicability have elicited interest. VGA-039 targets protein S, a potassium-dependent glycoprotein, synthesized in the liver, which has an inhibitory effect on clot formation. It acts as a co-factor for two anti-coagulatory proteins: protein C, a serine protease which, when activated, degrades the active forms of coagulation factors V and VIII, and tissue factor pathway inhibitor alpha, which inhibits the tissue factor-factor VIIa (TF-fVIIa) catalytic complex and prothrombinase.
It appears to play a controlling role, by rebalancing disruptions in coagulation that are associated with a variety of different causes. “We believe it can be a universal hemostatic therapy across a wide range of bleeding disorders,” Rosenthal said. The ASH presentation will include data on the ability of VGA-039 to restore thrombin generation and clot formation in a series of assays that mimicked the absence of von Willebrand factor, FVII, FVIII, FIX and FXIII. The antibody also increased fibrin deposition in the presence of a neutralizing anti-FVIII antibody.
A 2018 study, led by Anne Angelillo-Scherrer, at Bern University Hospital, in Switzerland, previously showed that targeting protein S in murine models of hemophilia improved coagulation. “That was part of the validation for going after this,” Rosenthal said.
Von Willebrand disease, which is usually inherited in an autosomal dominant fashion, is characterized by lifelong bleeding episodes and accompanying joint damage, although the severity of the condition can vary considerably. Unlike X-linked bleeding disorders such as hemophilia A and hemophilia B, it affects males and females with equal prevalence, but women can experience more severe symptoms, particularly during menstruation. They are also at a higher risk of mortality during childbirth.
Recombinant factor replacement therapy is available either for on-demand treatment or for reducing bleeding severity during surgery. Severe patients may require regular prophylaxis, which entails a twice-weekly infusion. In developing VGA-039, Vega has taken inspiration from Hemlibra (emicizumab), the bispecific antibody developed for hemophilia A by the Genentech arm of Basel, Switzerland-based Roche Holding AG and its majority-owned Tokyo-based subsidiary, Chugai Pharmaceutical Co. Ltd. Now a multibillion-dollar blockbuster, the product has allowed patients to eliminate or reduce the need for regular, time-consuming intravenous FVIII infusions. It can be self-administered by subcutaneous injection – dose schedules range from once weekly to once monthly. “It’s been transformational in people’s lives,” Rosenthal said.
Vega has similar ambitions for VGA-039, and it has already obtained supporting pharmacokinetic and pharmacodynamic data in nonhuman primates. The phase I study will enable it to track its activity even in healthy volunteers, before it can be tested in patients. “What’s nice is there are great biomarkers,” Rosenthal said. Thrombin generation and accumulation of d-dimer – a breakdown product arising from dissolved clots – can be readily measured.
The Vega team already has clocked up extensive experience in building a successful rare blood disorder program at True North Therapeutics. Early clinical data in cold agglutinin disease for an antibody targeting complement component 1s (C1s) prompted a buyout offer in 2017 of up to $825 million from Bioverativ, which Paris-based Sanofi SA then acquired for $11.6 billion. The True North antibody, now known as Enjaymo (sutimlimab), gained U.S. FDA approval earlier this year.
Vega, Rosenthal said, is “open-minded” about the commercial strategy for VGA-039. Its forthcoming debut at ASH has already prompted inward interest from a number of pharmaceutical firms. But the company is also positioning the program for the long term. “We’re developing this drug to take it all the way.”