On June 29, 2020 VITRAC Therapeutics, LLC (VITRAC) reported that initiated the global clinical development of VIC-1911, an oncology candidate formally known as TAS-119, which was licensed from Taiho Pharmaceutical Co., Ltd. (Taiho), a Japan-based oncology company (Press release, VITRAC Therapeutics, JUN 29, 2020, View Source [SID1234561547]). Two Phase-1 clinical studies have been conducted in the US and Europe by Taiho. VITRAC obtained an exclusive and global development and commercialization rights for TAS-119, and its IND has been successfully transferred to VITRAC in the US with a new code name, VIC-1911.

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"It is our honor to succeed the development of this drug that has been diligently developed by Taiho, and to be able to develop a potent Aurora A specific inhibitor, VIC-1911. This drug will give more treatment options to cancer patients since Aurora Kinase plays key oncogenic roles related to their mitotic activity, promote cancer cell survival, and proliferation," said Keizo Koya, Ph.D., President of VITRAC Therapeutics.

VITRAC also made an alliance with JS InnoMed Holdings (JSI) by sublicensing the China rights of VIC-1911 to accelerate the global development. "JSI is an amazing biopharmaceutical company filled with creative and distinguished scientists managed by a notable leader, Dr. Jintao Zhang. It is exciting to collaborate on a global scale towards the development of this drug with potential to ameliorate the lives of patients," said Dr. Koya.

On June 29, 2020 Aileron Therapeutics (NASDAQ:ALRN), a biotechnology company advancing a novel chemoprotective therapy for cancer patients, reported that it has enrolled the first patient in the open-label Phase 1b schedule optimization part of its ongoing Phase 1b/2 clinical trial, evaluating ALRN-6924’s potential to protect patients against chemotherapy-induced toxicities (Press release, Aileron Therapeutics, JUN 29, 2020, View Source [SID1234565066]). Patients in this open-label trial have p53-mutated extensive disease small cell lung cancer (SCLC) and are being treated with second-line topotecan following administration of ALRN-6924. The schedule optimization part of the trial is intended to determine whether ALRN-6924 given six hours before topotecan further enhances the protective effect of ALRN-6924 against severe hematological adverse events observed when ALRN-6924 was given 24 hours before topotecan in the dose optimization part of the trial, as reported by Aileron earlier this month.

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"Following our recent announcement of positive interim data from the Phase 1b dose optimization part of this ongoing Phase 1b/2 study, we are pleased to reach another key milestone in our advancement of ALRN-6924 to potentially transform the treatment paradigm for cancer patients undergoing chemotherapy," said Manuel Aivado, M.D., Ph.D., President & CEO of Aileron Therapeutics.

Dr. Aivado explained, "Chemotherapy remains a critical cornerstone treatment for millions of cancer patients. Unfortunately, in the process of killing cancer cells, chemotherapy inadvertently harms healthy cells, too. This leads to a multitude of common, damaging, severe toxicities. We treat healthy cells ahead of chemotherapy to prevent those toxicities, importantly, without interrupting chemotherapy’s potent onslaught against cancer cells. ALRN-6924 could dramatically improve patients’ quality of life by improving their tolerance to chemotherapy."

ALRN-6924’s novel mechanism of action leverages the innate ability of intracellular p53 protein to induce cell cycle arrest in healthy cells to prevent toxicities driven by chemotherapy’s off-target effects in bone marrow and potentially other tissues and organs. In patients with p53-mutant cancers, which represent approximately 50% of all cancer patients, ALRN-6924 is designed to shield healthy cells from chemotherapy while preserving the susceptibility of cancer cells to chemotherapy.

About the Phase 1b/2 Study

The ongoing Phase 1b/2 study is designed to identify an optimal dose and schedule of ALRN-6924 administration to reduce chemotherapy toxicities such as severe anemia, thrombocytopenia, and neutropenia caused by topotecan in patients with small cell lung cancer. There are two parts to the Phase 1b study: (i) dose optimization and (ii) schedule optimization.

In the dose optimization part, which enrolled 18 patients, ALRN-6924 was administered at three dose levels (0.3, 0.6, and 1.2 mg/kg) 24 hours before each dose of topotecan on days 1 through 5 of every 21-day treatment cycle. An expansion cohort of the dose optimization part of the trial at the 0.3 mg/kg dose level is ongoing.

Aileron announced positive interim findings from this part of the trial in June 2020. ALRN-6924 demonstrated a protective effect against severe chemotherapy-induced anemia and thrombocytopenia across all dose levels as compared to historical controls. In addition, patients treated with 0.3 mg/kg ALRN-6924 met the protocol-defined criteria for reduction of NCI CTC Grade 3/4 neutropenia to ≤50% in the first treatment cycle triggering the expansion cohort in up to eight patients.

In the schedule optimization part, ALRN-6924 is being administered at two dose levels (0.3 and 0.6 mg/kg) 6 hours before each dose of topotecan on days 1 through 5 of every 21-day treatment cycle. Aileron expects to enroll approximately 20 patients in this part of the study.
"We were highly encouraged by the strong chemoprotective effect of ALRN-6924 seen in the dose optimization part of this study as previously reported, as it reinforces our belief that ALRN-6924 can selectively induce cell cycle arrest to protect cancer patients from the toxic side effects of chemotherapy," said Vojo Vukovic, M.D., Ph.D., Chief Medical Officer of Aileron. "The schedule optimization part of the trial is intended to inform whether ALRN-6924 given six hours before topotecan can further enhance the protective effects we have observed when giving our drug 24 hours before topotecan."

Phase 1b/2 Trial – Next Steps

While enrollment in the 6-hour dosing schedule is underway, Aileron is continuing to enroll patients in the expansion cohort of its 0.3mg/kg dose level using the 24-hour schedule.

As previously reported, the company plans to report topline data from the schedule optimization and final data from the dose optimization parts of the trial in the fourth quarter of 2020. Aileron expects that these results will enable the company to determine a recommended ALRN-6924 dose and schedule for subsequent trials.

Aileron is carefully monitoring the effect of the coronavirus pandemic on its clinical trial sites and the healthcare system, which may impact the future timing of the trial and the company’s planned data announcements.

About ALRN-6924
ALRN-6924 is a first-in-class dual MDM2/MDMX inhibitor that is currently being evaluated in a Phase 1b/2 clinical trial as a chemoprotective agent to protect against chemotherapy-related toxicities.

On June 29, 2020 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that the U.S. Food and Drug Administration (FDA) has approved Roche’s Phesgo (pertuzumab, trastuzumab, and hyaluronidase-zzxf) injection, a fixed-dose combination (FDC) of Perjeta and Herceptin with Halozyme’s ENHANZE technology, administered subcutaneously in combination with intravenous (IV) chemotherapy, for the treatment of eligible patients with early and metastatic HER2-positive breast cancer (Press release, Halozyme, JUN 29, 2020, View Source [SID1234561532]). This is the first time a product has been approved combining two monoclonal antibodies that can be administered by a single subcutaneous injection utilizing Halozyme’s ENHANZE technology.

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"We are excited that HER2-positive breast cancer patients in the U.S. will now have the option to receive this important therapy in a meaningfully shorter period of time," said Dr. Helen Torley, president and chief executive officer. "This subcutaneous delivery was shown to be preferred to IV administration by 85% of patients in the PHranceSCa study due to less time in the clinic and more comfortable treatment administration. Phesgo is the second product to receive FDA approval this year, and the first demonstrating the ability to combine two monoclonal antibodies, utilizing our ENHANZE technology."

Phesgo is available in single-dose vials and can be administered in approximately eight minutes for the initial loading dose and approximately five minutes for each subsequent maintenance dose.(1) This is compared to approximately 150 minutes for a sequential infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions of the two medicines.(2,3) Phesgo can be administered by a healthcare professional in a treatment center or at a patient’s home.

The approval is based on results from the pivotal phase III FeDeriCa study, which met its primary endpoint, with Phesgo showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough), when compared to IV administration of Perjeta. The safety profile of Phesgo with chemotherapy was comparable to IV administration of Perjeta plus Herceptin and chemotherapy, and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhea and anemia.(1,4)

The phase II PHranceSCa study showed that 85% (136/160) of people receiving treatment for HER2-positive breast cancer preferred treatment under the skin to IV administration due to less time in the clinic and more comfortable treatment administration.(1)

About ENHANZE Technology
Halozyme’s proprietary ENHANZE drug-delivery technology is based on its patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration.

On June 29, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported that The Lancet Oncology published data from the NAVIGATOR clinical trial showing an unprecedented overall survival (OS) rate and a well-tolerated safety profile for AYVAKIT (avapritinib) in patients with advanced PDGFRA D842V mutant gastrointestinal stromal tumor (GIST) (Press release, Blueprint Medicines, JUN 29, 2020, View Source [SID1234561548]). The paper, titled "Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial," was published online in The Lancet Oncology on June 29, 2020.

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"The data published in The Lancet Oncology show that patients with PDGFRA D842V mutant GIST treated with AYVAKIT had deep and durable clinical responses as well as a high overall survival rate. These results represent a transformative advancement for patients whose tumor type is resistant to other approved therapies," said Michael Heinrich, M.D., Professor of Medicine at Oregon Health & Science University and primary author of the paper. "As a scientist who has dedicated my career to understanding the molecular basis of GIST and as a clinician treating patients, it’s tremendously rewarding to be able to offer – for the first time – a highly effective treatment option to my patients with PDGFRA D842V mutant GIST."

"Based on the compelling clinical data from the NAVIGATOR trial, AYVAKIT was granted a full approval by the FDA earlier this year and has become the new standard of care for patients with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "We are now focused on bringing AYVAKIT to additional patients with this genomically defined form of GIST in other geographies, including Europe."

Highlights from The Lancet Oncology Publication Data

The Lancet Oncology paper reported efficacy and safety results from the NAVIGATOR trial, including all patients enrolled in the dose escalation part of the trial and the subset of patients with PDGFRA D842V mutant GIST enrolled in the expansion part of the trial. The efficacy population comprised 56 patients with PDGFRA D842V mutant GIST. The safety population comprised 82 patients, including 26 patients with non-PDGFRA D842V mutant GIST enrolled in the dose escalation part of the trial. All results were as of a data cutoff date of November 16, 2018.

In patients with PDGFRA D842V mutant GIST, the overall response rate (ORR) was 88 percent (95% CI: 76-95%) with 9 percent of patients achieving a complete response. AYVAKIT demonstrated durable clinical benefit in this patient population with a 12-month duration of response rate of 70 percent (95% CI: 54-87%), a 12-month progression-free survival (PFS) rate of 81 percent (95% CI: 69-93%) and a 24-month OS rate of 81 percent (95% CI: 67-94%).

AYVAKIT was generally well-tolerated with most treatment-related adverse events (AEs) reported as Grade 1 or 2. The most common treatment-related AEs were nausea, fatigue, diarrhea, periorbital edema, anemia, decreased appetite, vomiting and memory impairment. Cognitive effects occurred in 40 percent of patients, with the majority of events reported as Grade 1.

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. AYVAKIT is the first precision therapy approved to treat a genomically defined population of patients with GIST and the only highly active treatment for PDGFRA exon 18 mutant GIST. The FDA granted Breakthrough Therapy Designation to avapritinib for the treatment of unresectable or metastatic GIST harboring the PDGFRA D842V mutation. For more information, visit AYVAKIT.com.

Avapritinib is not approved for the treatment of any other indication in the U.S. by the FDA or for any indication in any other jurisdiction by any other health authority.

Blueprint Medicines is developing avapritinib globally for the treatment of advanced, smoldering and indolent systemic mastocytosis (SM). The FDA granted Breakthrough Therapy Designation to avapritinib for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.

About GIST

GIST is a sarcoma, or tumor of bone or connective tissue, of the GI tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50 to 80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.

About 5 to 6 percent of primary GIST cases are caused by a PDGFRA D842V mutation, the most common PDGFRA exon 18 mutation. Prior to the approval of AYVAKIT, there were no highly effective treatments for PDGFRA D842V mutant GIST. Published data have shown poor outcomes in patients with PDGFRA D842V mutant GIST treated with imatinib and other approved therapies, including a median OS of 15 months, a median PFS of 3 months and an ORR of 0 percent.1

Important Safety Information

Intracranial hemorrhage (e.g., subdural hematoma, intracranial hemorrhage, and cerebral hemorrhage) occurred in 1% of 267 patients (0.7% Grade 3 or 4) with GIST and overall in 3% of 335 patients (1.2% Grade 3 or 4) who received AYVAKIT. Overall, 0.9% of patients receiving AYVAKIT required permanent discontinuation for an intracranial hemorrhage. Withhold AYVAKIT and then resume at a reduced dose upon resolution, or permanently discontinue AYVAKIT based on severity.

In 335 patients receiving AYVAKIT, CNS adverse reactions occurred overall in 58% of patients including cognitive impairment (41%; 3.6% Grade 3 or 4), dizziness (20%; 0.6% Grade 3 or 4), sleep disorders (15%; 0.3% Grade 3 or 4), mood disorders (13%; 1.5% Grade 3 or 4), speech disorders (6%; none Grade 3 or 4), and hallucinations (2.1%; none Grade 3 or 4). Overall, 3.9% of patients required permanent discontinuation of AYVAKIT for a CNS adverse reaction. Depending on severity, withhold AYVAKIT and then resume at the same dose or at a reduced dose upon improvement, or permanently discontinue AYVAKIT.

AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential and pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for two weeks after the final dose. Advise females and males of reproductive potential that AYVAKIT may impair fertility.

In 204 patients with unresectable or metastatic GIST, the most common adverse reactions (≥ 20%) were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash and dizziness.

Avoid coadministration of AYVAKIT with strong and moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong and moderate CYP3A inducers.

Please click here to see the full Prescribing Information for AYVAKIT.

On June 29, 2020 PharmEnable, a Cambridge-based drug discovery company using advanced medicinal chemistry and AI-enabled approaches to design the next generation of highly complex and specific drug candidate molecules, reported it has closed a £1.8 million seed financing to support its transition into a drug development company (Press release, PharmEnable, JUN 29, 2020, View Source [SID1234641051]). It aims to develop new treatments for conditions with significant unmet clinical need, by designing highly complex molecules for addressing challenging biological targets. The round, which was significantly over-subscribed, was led by Cambridge Enterprise, the commercialisation arm of the University of Cambridge, as well as the University of Cambridge Enterprise Fund VI, managed by Parkwalk Advisors. It also attracted support from a wealth of angel investors and notable life science funds, including Jonathan Milner, serial entrepreneur and founder of Abcam; Andy Richards, Cambridge-based entrepreneur and investor; David Ford, Oxford-based life sciences angel investor; the family office of Paul Forster, co-founder of Indeed.com; Ian Tomlinson, chairman of several bio-incubators, entrepreneur and co- founder of Domantis; KQ Labs at the Francis Crick Institute; Martlet Capital, a Cambridge-based investor with a growing portfolio of innovative life science companies; the fast-growing o2h ventures Human Health EIS fund; and Wren Capital, the established London-based angel investor in science, engineering and software businesses. A spin-out from the University of Cambridge in 2016, and financed to date by its founders and service-based revenues, PharmEnable will use the funding to evolve its business model and invest in a pipeline of drug discovery programmes across a number of disease areas including cancer and neurodegenerative disease. Additionally, PharmEnable will continue to engage in strategic partnerships with pharma, innovative biotechs and academia. PharmEnable is led by co-founder and CEO Dr Hannah Sore. It has attracted an experienced Board and management team including Dr Jane Dancer, previously of F-star, who joined recently as the new Board Chair. The financing has enabled PharmEnable to expand its scientific team including Dr David Vidal as Director of Technology, with further expansion, including the addition of a Director of Drug Discovery planned for Q3 2020. The PharmEnable platform technology can predict improved small molecule hits to targets across a range of disease areas. Its approach focuses on exploring and mapping the possible chemical universe and designing novel small molecules that are highly complex with shapes similar to those found in nature. This approach can identify hits with improved specificity compared with traditional screening methods, and allows PharmEnable to take on particularly challenging biological targets, such as protein-protein interactions and epitranscriptomic modifications that have been undruggable by existing approaches. Its solution consists of two elements: ChemUniverse a diversity-focused virtual database of chemically diverse molecules; and ChemSeek, a suite of gold standard AI-enabled tools for finding drug target matches from structure and ligand data.

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Commenting on the financing, CEO of PharmEnable Dr. Hannah Sore said:

"We are pleased to welcome on board our new investors and appreciate their confidence in our business. Our aim is to replicate the specificity of biologics in the powerful and scalable form of a small molecule, to treat devastating diseases where there are currently no treatment options. We have proven the strength of our platform in tapping unexplored parts of the chemical universe to find novel and specific hits for currently undruggable targets, and are excited to now be able to invest in our own pipeline of drug discovery programmes, as well as to develop further strategic partnerships."

Dr Christine Martin, Head of Life Science Investment at Cambridge Enterprise said:

"Cambridge Enterprise is really pleased to be investing in this exciting opportunity. To have closed the round during these last few months, and to have attracted such a strong investor syndicate, is a testament to the potential of the AI-enabled platform that PharmEnable has built. We are pleased to support the Company in its transition to in-house drug discovery. We believe the company will have significant impact through addressing undruggable therapeutic targets."

Following the investment, Dr Christine Martin, Head of Life Science Investment at Cambridge Enterprise and Peter McPartland, Investment Director of Martlet Capital and representative for all other investors, join the board of directors of PharmEnable, alongside Dr Jane Dancer (independent Chair), Dr Hannah Sore (CEO) Dr Natalia Mateu (CSO) and Gaynor Fryers (independent NED). David Ford also serves as a Board Observer for the entrepreneurs/angel investors.