On May 5, 2022 Anthos Therapeutics, a clinical-stage biopharma company developing innovative therapies for cardiovascular and metabolic diseases, reported that the first patient had been enrolled in a phase 3 clinical trial investigating a Factor XI agent (Press release, Anthos Therapeutics, MAY 5, 2022, View Source [SID1234613730]). The ASTER study is one of two complementary, international, multicenter trials where abelacimab is being studied in patients with Cancer Associated Thrombosis (CAT). In the ASTER trial, Anthos’ novel dual-acting Factor XI monoclonal antibody, abelacimab, is being compared to apixaban, the leading Factor Xa inhibitor, to assess their effects on venous thromboembolism (VTE) recurrence and bleeding in patients with cancer associated VTE.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Encouraged by evidence from a recently completed positive phase 2 study,1 we believe abelacimab could become an important new treatment option for the treatment and prevention of thrombosis in a variety of patients, including those with Cancer Associated Thrombosis. Abelacimab’s novel dual inhibitory activity offers the potential to provide effective antithrombotic activity with a reduced risk of bleeding compared to existing therapies. Additionally, the monthly dosing of abelacimab could reduce the burden of a daily regimen, such as daily injections or pills, for patients already receiving multiple therapies including chemotherapy," said Gary E. Raskob, Ph.D., Interim Senior Vice President, and Provost at the University of Oklahoma Health Sciences Center and the Chair of the Abelacimab CAT Program Steering Committee.

Venous Thromboembolism (VTE), which includes both deep vein thrombosis and pulmonary embolism, is the second most prevalent cause of death in patients with cancer, second only to the disease itself.2 However, treatment of CAT can be challenging because the currently available anticoagulants used to treat VTE can have an increased risk of bleeding.3,4

"An acute episode of thrombosis in patients with cancer adds additional complexity to the treatment of cancer itself and is a grave concern for physicians, patients, and caregivers. Our extensive phase 3 program for abelacimab includes two trials specifically designed for patients with Cancer Associated Thrombosis, including those with a particularly high risk of bleeding. Enrolling the first patients in the ASTER phase 3 trial is an important first step toward making an effective and potentially safer anticoagulant available to patients with cancer. This phase 3 program is in addition to our ongoing phase 2 AZALEA-TIMI 71 trial comparing abelacimab to rivaroxaban in atrial fibrillation (AF), which completed enrollment with 1,287 patients in December 2021. This study, the largest trial to date with a Factor XI inhibitor, will compare bleeding rates in AF patients treated with abelacimab and rivaroxaban," said Dan Bloomfield, M.D., Chief Medical Officer, Anthos Therapeutics.

About Abelacimab
Abelacimab is a novel, highly selective, fully human monoclonal antibody designed to induce effective hemostasis-sparing anticoagulation through Factor XI inhibition. Abelacimab targets the active domain of Factor XI, demonstrating dual inhibitory activity against both Factor XI and its activated form, Factor XIa. Abelacimab can be administered intravenously (IV) to achieve rapid inhibition of Factor XI activity and then used subcutaneously (SC) monthly to maintain nearly complete inhibition in a chronic setting. In a PK/PD study, abelacimab administered IV provided profound suppression of Factor XI within one hour after the start of therapy and maintained near maximal inhibition for up to 30 days. 1,5 In a Phase 2 study whose results were published in the New England Journal of Medicine in 2021, a single intravenous dose of abelacimab after knee surgery reduced the rate of venous thromboembolism by 80%, measured 10 days after surgery, compared to enoxaparin.1 Factor XI inhibition offers the promise of hemostasis-sparing anticoagulation for the prevention and treatment of arterial and venous thromboembolic events.6 Abelacimab is an investigational agent and has not been approved for any indication.

About the Abelacimab Phase 3 Program in Cancer Associated Thrombosis (CAT)
The abelacimab phase 3 CAT program comprises two complementary studies targeting to enroll approximately 2700 patients across 220 sites in more than 20 countries — the largest program of any anticoagulant performed in Cancer-Associated Thrombosis.

ASTER is an international multicenter, randomized, open-label, blinded endpoint evaluation, phase 3 study comparing the effect of abelacimab relative to apixaban on venous thromboembolism (VTE) recurrence and bleeding in patients with cancer associated VTE in whom DOAC treatment is recommended. Abelacimab 150 mg will be administered intravenously (IV) on Day 1 and subcutaneously (SC) monthly thereafter for up to 6 months; Apixaban 10 mg will be administered orally, twice daily (bid) for the first 7 days, followed by 5 mg bid up to 6 months.

MAGNOLIA is an international multicenter, randomized, open-label, blinded endpoint evaluation, phase 3 study in patients with gastrointestinal (GI) / genitourinary (GU) cancer in whom DOAC treatment is not recommended. The study will compare the effect of abelacimab relative to dalteparin on VTE recurrence and bleeding in patients with cancer associated VTE who are at a high bleeding risk with non-resectable, locally or regionally invasive GI / GU tumors. Abelacimab 150 mg will be administered intravenously (IV) on Day 1 and subcutaneously (SC) monthly thereafter for up to 6 months; dalteparin administered subcutaneously will be given daily, 200 IU/kg/day for the first month, and then 150 IU/kg/day up to 6 months.

About the AZALEA-TIMI 71 Phase 2 Trial
The AZALEA-TIMI 71 trial is an event-driven, randomized, active-controlled, blinded endpoint, parallel-group study to evaluate the effect of two blinded doses of abelacimab relative to open label rivaroxaban on the rate of major or clinically relevant non-major (CRNM) bleeding events in patients with atrial fibrillation (AF) who are at moderate-to-high risk of stroke. The trial completed enrollment in December 2021, with 1287 patients across 95 global study sites including the U.S., Canada, as well as from parts of Europe, and Asia.

Verhamme P et al. New Engl J Med July 2021 (View Source)
Fernandes CJ et al. Eur. Resp. Rev. 2019 (View Source)
Agnelli G et al. New Engl J Med April 2020 (View Source)
Abdol Razak NB et al. Cancers (Basel) Oct. 2018 (View Source)
Yi BA et al. J Thromb Haemost. Oct. 2021 (View Source)
Hsu et al. J Am Coll Cardiol. Aug. 2021 (https://www.sciencedirect.com/science/article/abs/pii/S0735109721053213?via%3Dihub)

On May 5, 2022 Aravive, Inc. (Nasdaq: ARAV), a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease, reported that it will host a Key Opinion Leader (KOL) Symposium on the GAS6-AXL signaling pathway and the Company’s lead drug candidate, batiraxcept (Press release, Aravive, MAY 5, 2022, View Source [SID1234613756]). Senior management will also provide updates on Aravive’s clinical development programs. The event will take place on May 11, 2022, from 8:00 am ET to 12:00 pm ET and will include a live and archived webcast at: View Source

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The anticipated KOL Symposium schedule (all times are ET):

8:50 am – 9:00 am Opening Remarks
Gail McIntyre, Ph.D.; Aravive CEO and Director

9:00 am – 9:30 am Overview of the TAM Kinases:
Amato Giaccia, Ph.D.; Aravive Founder and Director Director, MRC Oxford Institute for Radiation Oncology Jack, Lulu and Sam Wilson Professor of Radiation Oncology, Emeritus, Stanford University

9:30 am – 10:00 am Batiraxcept in PROC:
Katherine Fuh, M.D., Ph.D.; Gynecologic Oncologist & Associate Professor Division of Gynecologic Oncology, Washington University, Siteman Cancer Center

10:00 am – 10:30 am Batiraxcept in ccRCC:
Brian Rini, M.D.; Chief of Clinical Trials, Vanderbilt-Ingram Cancer Center & Professor of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center

10:30 am – 11:00 am Batiraxcept in Pancreatic Adenocarcinoma:
Paul Oberstein, M.D., M.S.; Associate Professor of Medicine and Director of Gastrointestinal Medical Oncology, Perlmutter Comprehensive Cancer Center, NYU Langone Health

11:00 am – 11:15 am Program Updates

11:15 am – 12:00 pm Panel Discussion and Q&A

On May 5, 2022 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical-stage radiopharmaceutical company developing next-generation products to address the growing needs in oncology, reported that confirms Clarity and its clinical development programs are unaffected by Novartis’ recent suspension of production of Lutathera and Pluvicto/ 177Lu-PSMA-617 at its facilities in Ivrea, Italy and Millburn, New Jersey (Press release, Clarity Pharmaceuticals, MAY 5, 2022, View Source [SID1234614044]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On 5 May 2022, Novartis released an update regarding the suspension due to potential quality issues identified in its manufacturing processes and expects a resolution of these issues, and resumption of some supply, in the next 6 weeks. The production suspension impacts commercial and clinical trial supply as Novartis put a temporary hold on screening and enrollment for 177Lu-PSMA-617 clinical trials globally, and Lutathera clinical trials in the US and Canada.1

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "Clarity and our clinical development programs are not impacted by the Novartis production disruption as our Targeted Copper Theranostics (TCTs) are wholly independent of the Lutathera and Pluvicto supply chains and other first generation radiopharmaceuticals."

"Our greatest concern at this time is for the patients who need these important products now, and we hope that Novartis can re-commence supply shortly. As we have seen to date, the biggest threat to radiopharmaceuticals is not the efficacy of radiopharmaceutical products, but the ongoing sustainable supply of these products to patients. It has been known for many decades that radiation is a powerful weapon in the management and treatment of cancer; however, the lack of secure supply jeopardises market acceptance and confidence of clinicians and patients in these therapies," Dr Taylor added.

TCTs employ copper-64 (Cu-64) and copper-67 (Cu-67) for diagnosis and therapy respectively utilising proprietary SAR technology. TCTs are a next-generation disruptive platform in radiopharmaceuticals, which delivers a compelling combination of high accuracy and high precision in the treatment of a range of cancers, while providing supply and logistical advantages over current theranostics.

Cu-67 is produced domestically in the US on electron accelerators with high purity and high specific activity and Cu-64 is produced on cyclotrons around the world. Both isotopes have half-lives that favour centralised manufacture and broad distribution. The TCT platform also has a number of environmental benefits, including the clean production of isotopes without the creation of highly toxic and long-lived waste products during manufacture.

Utilising the many benefits of Clarity’s SAR technology, all TCT products are manufactured at room temperature, significantly lowering the risk of batch failures, in contrast to first generation radiopharmaceuticals, including Lu-177 based products, which require heating the biological targeting agents to 90°C during manufacture. Furthermore, as the majority of nuclear reactors are located outside of the US2, reactor based radiopharmaceuticals also require long transit times into the US from other jurisdictions.

In recent times, a number of complications have arisen with nuclear reactor produced radiopharmaceuticals, most recently being the outage at the High Flux Reactor (HFR) in Petten, Netherlands, in February 20223,4,5,6. The EU has flagged this as a significant issue and advised that the European research reactors are approaching their "end-of-life". Without replacing this aging infrastructure, the EU could experience significant radioisotope shortages and impede access to vital treatments for its citizens. These shortages may impact the roll-out of lutetium-177 (177Lu) based products, which will severely hinder the growth of radiopharmaceuticals moving forward.7

"Clarity’s TCT platform of products aims to minimise all of these risks by clearly differentiating ourselves from the current pack of first generation radiopharmaceuticals and fully exploiting the many benefits of the "perfect pairing" of copper isotopes, including security and control of the entire supply chain, as we advance towards our ultimate goal of better treating children and adults with cancer," Dr Taylor concluded.

On May 5, 2022 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a clinical-stage precision oncology company designing and developing novel targeted therapies for cancer treatment, reported that it has entered into an exclusive license agreement with LaNova Medicines Limited (LaNova) to develop and commercialize LM-302, a novel antibody drug conjugate (ADC) targeting Claudin18.2, in the U.S. and rest of the world, excluding Greater China and South Korea (Press release, Turning Point Therapeutics, MAY 5, 2022, View Source [SID1234614124]). Claudin18.2 is a protein expressed in many gastrointestinal cancers, including gastric, gastroesophageal junction and pancreatic cancer. LM-302, which going forward will be identified as TPX-4589, is currently in Phase 1 clinical trials in both the U.S. and China.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the terms of the licensing agreement, LaNova will receive an upfront payment of $25 million and will be eligible to receive up to an additional $195 million in development and regulatory milestone payments; in addition, LaNova is eligible to receive commercial sales milestones, and tiered royalties ranging from mid-single digit to mid-teens percentages on net sales (subject to customary deductions). As part of the agreement, both parties agreed to potentially broaden the partnership by collaborating on up to three additional ADC programs.

TPX-4589 (LM-302) is a potentially first-in-class anti-Claudin18.2 ADC discovered by LaNova that suppresses cell proliferation of gastric and pancreatic cell lines with nanomolar potency in preclinical models. It also has demonstrated efficacy in gastric and pancreatic cancer xenograft models.

"We are excited to announce our first in-license as a company and strategically expand our clinical stage portfolio, specifically within GI tumors. Claudin18.2 is continuing to emerge as an important target," said Athena Countouriotis, M.D., President and Chief Executive Officer of Turning Point. "We chose TPX-4589 based on it potentially being a first-in-class ADC to target Claudin18.2 and its preclinical data that show the potential to target tumors with low and high expression levels, which we believe could be an important differentiator versus other investigational therapies."

"LaNova Medicines is focused on discovery and development of innovative medicines in oncology. We are very pleased to partner with Turning Point for LM-302, an innovative drug molecule with the potential as a novel treatment for gastric and pancreatic cancers. This partnership is an example of our discovery and development capabilities and our ambition for global innovation and patients," said Dr. Crystal Qin, Chairman and CEO of LaNova.

It is estimated that the annual incidence of gastric and gastroesophageal junction cancers in the U.S. and EU5 is approximately 27,000 and 50,000, respectively1. The estimated annual incidence of pancreatic cancer in the U.S. and EU5 is approximately 60,000 and 70,000, respectively1. Approximately 65% of patients in pancreatic2, gastric and gastroesophageal junction3 cancers have tumors that express Claudin18.2.

Webcast/Conference Call Information
Turning Point will host a webcast and conference call on May 5, 2022 at 6 p.m. ET / 3 p.m. PT to discuss this announcement. Athena Countouriotis, M.D., President and Chief Executive Officer, will host the virtual event for investors and will be joined by Kumar Srinivasan, Chief Business Officer.

The event will be accessible through the "Investors" section of www.tptherapeutics.com or by dialing (844) 256-2297 (in the United States) or (236) 714-3006 (outside the U.S.) using conference ID 8780394. A replay will be available shortly after the live event through the "Investors" section of www.tptherapeutics.com.

On May 5, 2022 Novartis reported the European Commission (EC) has approved Jakavi (ruxolitinib) for the treatment of patients aged 12 years and older with acute or chronic GvHD who have inadequate response to corticosteroids or other systemic therapies (Press release, Novartis, MAY 5, 2022, View Source [SID1234614189]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Today, 30-60% of patients with GvHD do not respond to first-line steroid treatment, underscoring the need for new approaches to ensure long-term treatment goals are met," said Dr. Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany. "The approval of Jakavi offers healthcare providers and patients with GvHD who remain dependent on or refractory to steroids a new way to manage this debilitating and life-threatening condition."

The approval of Jakavi follows the positive opinion granted in March by the Committee for Medicinal Products for Human Use of the European Medicines Agency, based on the Phase III REACH2 and REACH3 trials in which Jakavi demonstrated superiority in overall response rate (ORR) compared to best available therapy (BAT). Results of REACH2 showed 62% ORR with Jakavi at Day 28, compared to 39% for BAT; and REACH3 demonstrated a significantly improved ORR at week 24 (50% vs. 26%) with a higher best ORR (76% vs. 60%) vs. BAT, among steroid-refractory/dependent chronic GvHD patients2,3.

"Five out of ten patients who receive allogeneic stem cell transplants experience the serious and sometimes fatal symptoms of graft-versus-host disease," says Marie-France Tschudin, Novartis President of Innovative Medicines International and Chief Commercial Officer. "Jakavi, with this new indication in GvHD, will help to redefine treatment for patients who do not respond to first-line care."

GvHD occurs when donor cells see the recipient’s healthy cells as foreign and attack them. Symptoms of GvHD can appear in the skin, gastrointestinal tract, liver, mouth, eyes, genitals, lungs and joints. Approximately 50% of allogeneic stem cell transplant recipients will develop either acute or chronic GvHD. Both acute and chronic GvHD can be fatal and until now both have lacked an established standard of care for patients who do not adequately respond to first-line steroid treatment1,4-9. Currently, there are no other approved therapies for the treatment of GvHD after steroid failures1,2.

About Jakavi (ruxolitinib)
Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease- related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF, and also for patients aged 12 years and older with acute or chronic GvHD who have inadequate response to corticosteroids or other systemic therapies. Jakavi is approved in over 100 countries for patients with MF, including EU countries, Switzerland, Canada, Japan and in more than 85 countries for patients with PV, including EU countries, Switzerland, Japan and Canada. The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.

Novartis licensed ruxolitinib from Incyte for development and commercialization outside the United States. Ruxolitinib is marketed in the United States by Incyte as Jakafi for adults with PV who have had an inadequate response to or are intolerant of hydroxyurea, for adults with intermediate or high-risk MF, for adult and pediatric patients 12 years and older with steroid-refractory acute GvHD, and adult and pediatric patients 12 years and older with chronic GvHD after failure of one or two lines of corticosteroids or other systemic therapy.

Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte. The safety and efficacy profile of Jakavi has not yet been established outside of its approved indications.