On May 14, 2024 Instylla, Inc., a privately held clinical-stage company focused on developing liquid embolics for peripheral vascular embolotherapy, reported the completion of patient enrollment in the ongoing Instylla HES Hypervascular Tumor Pivotal Study (Press release, Instylla, MAY 14, 2024, View Source [SID1234643193]).

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The Instylla HES Hypervascular Tumor Pivotal Study is a prospective, multicenter, randomized clinical study to evaluate the safety and effectiveness of Instylla’s Embrace Hydrogel Embolic System (HES) compared with standard of care transcatheter arterial embolization or transcatheter arterial chemoembolization for the vascular occlusion of hypervascular tumors. A wide variety of tumors were treated in the study including primary and metastatic liver tumors, metastatic bone tumors, and renal tumors.
Dr. Nadine Abi-Jaoudeh, the study’s National Principal Investigator and Chief of Interventional Radiology at the University of California, Irvine, said, "Congratulations to all the investigators, study coordinators, and the Instylla team on the completion of enrollment for the Instylla HES Hypervascular Tumor Pivotal Study. This marks an exciting milestone in the field of embolization of hypervascular tumors. We hope the study will be positive and demonstrate that this next-generation liquid embolic technology will improve the lives of our patients who have to navigate their challenging clinical conditions. We want to thank all the patients that participated."

"Enrollment completion represents a significant milestone for Instylla and cancer patients diagnosed with hypervascular tumors," said Amar Sawhney, CEO of Instylla, Inc. and Managing Director of Incept, LLC. "We look forward to continuing to work with the study investigators to maintain the high quality of patient follow-up as we continue on our pathway to a PMA for Embrace HES."

About Embrace Hydrogel Embolic System:
Embrace HES is an investigational device intended to embolize hypervascular tumors in vessels ≤ 5 mm. Embrace HES consists of two injectable liquid precursors that solidify when simultaneously delivered into blood vessels, forming a soft hydrogel that fills the vessel lumens during embolization. The Embrace HES embolization uses no organic solvents, does not need sizing to the vessel diameter, and eliminates the possibility of catheter entrapment. Its main components are water and polyethylene glycol (PEG).

On May 14, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported the initiation of a Phase II/III trial to evaluate the efficacy of a combination of the HUTCHMED drug candidate surufatinib, the Jiangsu Hengrui Pharmaceuticals Co., Ltd ("Hengrui Pharma") PD-1 antibody camrelizumab, nab-paclitaxel and gemcitabine as a first-line treatment for patients with metastatic pancreatic ductal adenocarcinoma ("PDAC") in China (Press release, Hutchison China MediTech, MAY 14, 2024, View Source [SID1234643170]). PDAC is an exocrine tumor and the most common form of pancreatic cancer. The first patient received the first dose on May 8, 2024.

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PDAC is a highly aggressive form of cancer, representing over 90% of pancreatic cancer cases. Globally, an estimated 511,000 people were diagnosed with pancreatic cancer, leading to approximately 467,000 deaths in 2022, with an average five-year survival rate of less than 10%. In China, an estimated 119,000 people were diagnosed with pancreatic cancer, causing approximately 106,000 deaths in 2022.[1] Treatments such as chemotherapy, surgery and radiation are commonly employed, but have not shown significant improvement in patient outcomes. Under 20% of metastatic pancreatic cancer patients survive more than a year.[ii]

The trial is a multicenter, randomized, open-label, active-controlled, Phase II/III trial to evaluate the efficacy and safety of surufatinib combined with camrelizumab, nab-paclitaxel, and gemcitabine versus nab-paclitaxel plus gemcitabine as a treatment for adults with metastatic pancreatic cancer who have not been previously treated with a systemic anti-tumor therapy. After an initial safety run-in stage, the Phase II/III stage of the study may enroll a further 500 patients, with a primary endpoint of overall survival (OS). Other endpoints include objective response rate (ORR), progression free survival (PFS), disease control rate (DCR), safety, quality of life, duration of response and time to response. Additional details may be found at clinicaltrials.gov, using identifier NCT06361888.

Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said, "Emerging data including those from an investigator-initiated study presented at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, demonstrated that combinations of surufatinib, camrelizumab and chemotherapy have promising efficacy in comparison with existing chemotherapy-based treatments in metastatic PDAC.[3] We hope that this partnership will enable us to bring new, potentially life-changing treatment options to patients."

About Surufatinib
Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

Surufatinib is marketed in China by HUTCHMED under the brand name SULANDA, and was first included in the China National Reimbursement Drug List (NRDL) in January 2022 for the treatment of non-pancreatic and pancreatic neuroendocrine tumors (NETs).

About Camrelizumab
Camrelizumab (SHR-1210) is a humanized monoclonal antibody targeting the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Currently, more than 10 clinical trials are underway worldwide in a broad range of tumors and treatment settings.

Camrelizumab, under the brand name AiRuiKa, is currently approved for nine indications in China, including hepatocellular carcinoma ("HCC") (second-line and first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma, and nasopharyngeal carcinoma in the first-line setting. All indications have been included in China’s national medical insurance catalog, making it the leading domestic PD-1 product in terms of approved indications and tumor types covered. The U.S. Food and Drug Administration ("FDA") granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021, and accepted a New Drug Application (NDA) for camrelizumab and rivoceranib as a first-line therapy for unresectable HCC, with FDA Prescription Drug User Fee Act (PDUFA) dates in May 2024.

On May 14, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that it has initiated a registrational Phase III clinical trial of HMPL-306 in patients with mutated isocitrate dehydrogenase ("IDH") 1 or 2 relapsed / refractory acute myeloid leukemia ("AML") in China (Press release, Hutchison China MediTech, MAY 14, 2024, View Source [SID1234643169]). The first patient received their first dose on May 11, 2024.

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HMPL-306 is a novel dual-inhibitor of IDH1 and IDH2 enzymes. Mutations of IDH1 and IDH2 have been implicated as drivers of certain hematological malignancies, gliomas and solid tumors, particularly among AML patients. Although some IDH inhibitors have been approved in certain markets for AML, isoform switching between the cytoplasmic mutant IDH1 and mitochondrial mutant IDH2 often leads to acquired resistance to single inhibitors of IDH1 or IDH2. Targeting both IDH1 and IDH2 mutations may provide therapeutic benefits in cancer patients by overcoming this acquired resistance.

RAPHAEL is a multicenter, randomized, open-label, registrational Phase III clinical trial designed to evaluate the safety and efficacy of HMPL-306 as a monotherapy in patients with relapsed or refractory AML harboring IDH1 and/or IDH2 mutations. The primary endpoint of overall survival (OS) and the secondary endpoints, including event-free survival (EFS) and complete remission ("CR") rate, will be tested in comparison with current salvage chemotherapy regimens. The Company is looking to enroll approximately 320 patients for this registrational study, which is being led by principal investigator Prof Xiaojun Huang of Peking University People’s Hospital. Additional details may be found at clinicaltrials.gov, using identifier NCT06387069.

The study follows positive data from a two-stage, open-label Phase I study evaluating the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL-306 in this indication (NCT04272957). The first-in-human dose-escalation stage data was presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress ("EHA") in June 2023.[1] Results of the dose expansion stage of the study in over 50 patients demonstrated promising CR rates at the recommended Phase II dose are expected to be presented at the EHA (Free EHA Whitepaper) Congress in June 2024.

About IDH and Hematological Malignancies
IDHs are critical metabolic enzymes that help to break down nutrients and generate energy for cells. When mutated, IDH creates a molecule that alters the cell’s genetic programming and prevents cells from maturing. IDH1 or IDH2 mutations are common genetic alterations in various types of blood and solid tumors, including AML with approximately 14-20% of patients having mutant IDH genes, myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), low-grade glioma and intrahepatic cholangiocarcinoma. Mutant IDH isoform switching, either from cytoplasmic mutant IDH1 to mitochondrial mutant IDH2, or vice versa, is a mechanism of acquired resistance to IDH inhibition in AML and cholangiocarcinoma.[2],[3],[4]

According to the National Cancer Institute (NCI), there will be approximately 20,380 new cases of AML in the U.S. in 2023 and the five-year relative survival rate is 31.7%[5]. Currently, the U.S. Food and Drug Administration (FDA) has approved two drugs for IDH1 mutation and one drug for IDH2 mutation, but no dual inhibitor targeting both IDH1 and IDH2 mutants has been approved. There were an estimated 19,700 new cases of AML in China in 2018 and is estimated to reach 24,200 in China in 2030.[6] In China one IDH1 inhibitor was approved in 2022.

On May 13, 2024 Apellis Pharmaceuticals, Inc. (the "Company") reported to have entered into a financing agreement (the "Financing Agreement") with the guarantors party thereto, the lenders party thereto (the "Lenders"), and Sixth Street Lending Partners, as the administrative agent and collateral agent for the Lenders (Filing, 8-K, Apellis Pharmaceuticals, MAY 13, 2024, View Source [SID1234643207]). The Financing Agreement provides for a senior secured term loan facility of up to $475 million (the "Credit Facility"), consisting of an initial draw of $375 million at closing and a potential additional $100 million draw at the Company’s option upon satisfaction of a $50 million minimum cash requirement and a requirement that the Company’s trailing three-month sales of SYFOVRE were at least $180 million prior to the $100 million draw. The Credit Facility matures on May 13, 2030 (the "Maturity Date") and bears interest at an annual rate equal to the 3-month Secured Overnight Financing Rate (SOFR) + 5.75% (subject to 1.00% floor). Certain additional commitment and undrawn amount fees are also payable in connection with the Credit Facility.

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Apellis used the majority of the proceeds of the $375 million draw at closing to buy out its remaining obligations owed to SFJ Pharmaceuticals ("SFJ"), in the amount of approximately $326 million. The buyout of the SFJ development liability will eliminate $366 million in payments owed to SFJ, including approximately $200 million owed through 2025.

The Credit Facility does not provide for scheduled amortization payments during the term. All principal will be due on the Maturity Date. The Company will have the right to prepay loans under the Credit Facility at any time. The Company is required to repay loans under the Credit Facility with proceeds from certain asset sales, condemnation events and extraordinary receipts, subject, in some cases, to reinvestment rights. Repayments are subject to a prepayment premium.

All obligations under the Financing Agreement will be secured on a first-priority basis, subject to certain exceptions, by security interests in substantially all assets of the Company and material subsidiaries of the Company, including its intellectual property, and will be guaranteed by material subsidiaries of the Company, including foreign subsidiaries, subject to certain exceptions.

The Financing Agreement contains customary covenants, including, without limitation, a financial covenant to maintain liquidity of at least $50 million if the Company’s market capitalization is below $3 billion, and negative covenants that, subject to certain exceptions, restrict indebtedness, liens, investments (including acquisitions), fundamental changes, asset sales and licensing transactions, dividends, modifications to material agreements, payment of subordinated indebtedness, and other matters customarily restricted in such agreements. Among other permissions, the Company is permitted, on terms and conditions set forth on the Financing Agreement, to enter into a separate asset-based financing arrangement with a third party in an amount of up to $100 million, which amount is increased to $200 million upon certain sales or market capitalization thresholds, and to have outstanding convertible unsecured notes in an amount equal to the greater of $400 million and 10% of the Company’s market capitalization, but not to exceed $600 million. The Company is subject to restrictions on sales and licensing transactions with respect to its core intellectual property, defined to include SYFOVRE, EMPAVELI, and other pegcetacoplan product assets, subject to certain exceptions, including certain transactions related to areas outside the United States and Europe.

The Financing Agreement also contains certain events of default after which loans under the Credit Facility may be due and payable immediately, including payment defaults, material inaccuracy of representations and warranties, covenant defaults, bankruptcy and insolvency proceedings, cross-defaults to certain other agreements, judgments against the Company and its subsidiaries, and change of control.

The above description of the Financing Agreement and Credit Facility is a summary only and is qualified in its entirety by reference to the Financing Agreement, which will be filed as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ending June 30, 2024.

On May 13, 2024 Ajax Therapeutics, Inc., a biopharmaceutical company developing next generation JAK inhibitors for patients with myeloproliferative neoplasms (MPNs), reported the closing of an oversubscribed $95 million Series C financing (Press release, Ajax Therapeutics, MAY 13, 2024, View Source [SID1234643180]). Proceeds from the financing will be used to support the clinical development of Ajax’s first-in-class Type II JAK2 inhibitor, AJ1‑11095, for the treatment of myelofibrosis, as well as advancing the company’s pipeline of treatments for MPNs.

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The financing was led by Goldman Sachs Alternatives with participation by Eli Lilly and Company, Vivo Capital, RA Capital Management, Point72 and existing investors EcoR1 Capital, Boxer Capital, Schrödinger, Inc. and Inning One Ventures. Concurrent with the financing, Amit Sinha, Head of Life Sciences Investing and Ming Cheah, PhD, Vice President, within Life Sciences Investing at Goldman Sachs Alternatives, joined Ajax’s board of directors.

"We’re pleased to have attracted this level of support from such distinguished life sciences investors and biopharmaceutical companies in addition to our existing investor syndicate," said Martin Vogelbaum, co-founder and CEO of Ajax Therapeutics. "We are now well positioned to bring much needed innovation to the field of JAK inhibitors for the treatment of MPNs and look forward to advancing AJ1‑11095 into the clinic for myelofibrosis later this year."

AJ1-11095 was designed by Ajax, through our collaboration with Schrödinger, using structure-based drug design and computational methods at scale, to selectively bind the Type II conformation of the JAK2 kinase and to provide greater efficacy with disease modification compared to all currently approved JAK2 inhibitors which bind the Type I conformation of JAK2. Additionally, AJ1-11095 has been shown in preclinical studies to maintain efficacy against MPN cells that become resistant to chronic Type I JAK2 inhibition.

"Despite significant advances brought by the introduction of JAK inhibitors, patients with MPNs continue to have major unmet needs as current therapies, including Type I JAK2 inhibitors, often fail to provide adequate symptomatic relief and have little effect on the underlying disease," said Amit Sinha, Head of Life Sciences Investing at Goldman Sachs Alternatives. "We look forward to working with Ajax’s management team to bring novel therapies, such as AJ1-11095, to patients with myelofibrosis."

"JAK2 overactivation is central to the pathogenesis of MPNs and a Type II JAK2 inhibitor has the potential to address MPNs beyond myelofibrosis, including patients with polycythemia vera and essential thrombocythemia" said Ming Cheah, a Vice President in Life Sciences Investing at Goldman Sachs Alternatives. "We are proud to support the Company in delivering a new generation of transformational treatments for MPN patients."

"This financing reinforces the value of Ajax’s approach to inhibiting JAK2 with its Type II inhibitor, AJ1-11095," said Dr. Ross Levine, Ajax co-founder and Chair of Ajax’s Scientific Advisory Board, Senior Vice President for MH Translational Research and Member of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center. "My lab has been studying Type II inhibition of JAK2 for over 10 years and we believe AJ1-11095 possesses the unique therapeutic properties and disease modifying effects of a highly selective and potent Type II JAK2 inhibitor and we’re excited to bring it to patients with MF."