Blueprint Medicines Announces Publication in The Lancet Oncology Showing Durable Clinical Benefits of AYVAKIT™ (avapritinib) in NAVIGATOR Trial Patients with PDGFRA D842V Mutant GIST

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.

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 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.

VITRAC Therapeutics Initiated Global Clinical Development of VIC-1911, licensed from Taiho Pharmaceutical

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.

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!

"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.

Arya Sciences Acquisition Corp. Shareholders Approve Business Combination Transaction with Immatics

On June 29, 2020 Arya Sciences Acquisition Corp. (NASDAQ: ARYA or "Arya"), a special purpose acquisition company sponsored by Perceptive Advisors, and Immatics Biotechnologies GmbH ("Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell redirecting cancer immunotherapies, reported that its respective shareholders approved the business combination between Arya and Immatics announced on March 17, 2020 (Press release, Arya Sciences, JUN 29, 2020, View Source [SID1234561546]). None of Arya’s shareholders redeemed their shares in connection with the ARYA shareholder approval. The respective boards of directors of both Arya and Immatics had previously approved the business combination.

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!

Following the Arya shareholder vote, Immatics and Arya commenced final procedures towards the closing of the business combination and expect the closing to be completed in the coming days. It is further expected that the trading of the shares of the combined company, called Immatics N.V., will commence under the symbol "IMTX" on the first trading day thereafter. Immatics will continue to operate under its existing management team led by Chief Executive Officer, Harpreet Singh, Ph.D.

About the Transaction
On March 17, 2020, Immatics entered into a definite business combination agreement with Arya and in connection with the entry into the business combination agreement, a group of leading U.S. healthcare institutional investors committed to invest in Immatics N.V. through an ordinary share private investment in public equity ("PIPE"). Immatics shareholders, Arya shareholders and the PIPE investors will hold shares in Immatics N.V.

Advisors
Goldman Sachs International is acting as lead financial advisor with SVB Leerink, BofA Securities and Kempen serving as financial advisors to Immatics. Jefferies LLC is acting as lead financial and capital markets advisor to Arya as well as sole private placement agent. Chardan Capital Markets LLC is also serving as advisor to Arya. Goodwin Procter LLP and CMS Legal Services EEIG are acting as legal counsel to Immatics. Kirkland & Ellis LLP is serving as legal counsel to Arya.

Seattle Genetics Announces Positive Topline Results from Phase 2 Clinical Trial of Tisotumab Vedotin in Recurrent or Metastatic Cervical Cancer

On June 29, 2020 Seattle Genetics, Inc. (Nasdaq:SGEN) reported positive topline results from the phase 2 single-arm clinical trial known as innovaTV 204 evaluating tisotumab vedotin administered every three weeks for the treatment of patients who have relapsed or progressed on or after prior treatment for recurrent or metastatic cervical cancer (Press release, Seattle Genetics, JUN 29, 2020, View Source [SID1234561545]). Results from the trial showed a 24 percent confirmed objective response rate (ORR) by independent central review [95% Confidence Interval: 15.9%-33.3%] with a median duration of response (DOR) of 8.3 months. The most common treatment-related adverse events (greater than or equal to 20 percent) included alopecia, epistaxis (nose bleeds), nausea, conjunctivitis, fatigue and dry eye. The data will be submitted for presentation at an upcoming medical meeting.

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!

Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) directed to tissue factor, which is expressed on cervical cancer and can promote tumor growth, angiogenesis and metastases.1 Standard therapies for previously treated recurrent and/or metastatic cervical cancer generally result in limited objective response rates of typically less than 15 percent with median overall survival ranging from 6.0 to 9.4 months, in an all-comers population.1-8 Tisotumab vedotin is being developed by Seattle Genetics in collaboration with Genmab.

"Available therapies upon progression after first line chemotherapy in recurrent or metastatic cervical cancer are limited, and there is a significant unmet need for new treatment options," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "Tisotumab vedotin has demonstrated clinically meaningful and durable objective responses with a manageable safety profile, and we look forward to discussing with the FDA the potential submission of a Biologics License Application to support an accelerated approval."

Cervical cancer originates in the cells lining the cervix. Over 13,500 women are expected to be diagnosed with cervical cancer in the U.S. in 2020, with approximately 4,200 deaths.9 Cervical cancer remains one of the leading causes of cancer death in women globally, with over 311,000 women dying annually; the vast majority of these women being in the developing world.10 Routine medical examinations and the human papillomavirus (HPV) vaccine have lowered the incidence of cervical cancer in the developed world. Despite these advances, women are still diagnosed with cervical cancer, which often recurs or becomes metastatic.

Additional clinical trials of tisotumab vedotin are currently enrolling patients, including in combination with pembrolizumab, carboplatin or bevacizumab, and with a weekly dosing schedule in patients with locally advanced or metastatic cervical cancer. Tisotumab vedotin is also being evaluated in other tissue factor expressing tumor types, including ovarian and other solid tumors.

About innovaTV 204 Trial

The innovaTV 204 trial (also known as GCT1015-04 or innovaTV 204/GOG-3023/ENGOT-cx6) is an ongoing single-arm, global, multicenter study of tisotumab vedotin for patients with recurrent or metastatic cervical cancer who were previously treated with doublet chemotherapy with or without bevacizumab. Additionally, patients were eligible if they had received up to two prior lines of therapy in the metastatic setting. In the study, 101 patients were treated with tisotumab vedotin at multiple centers in the U.S. and Europe. The primary endpoint of the trial was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by independent central review. Key secondary endpoints included duration of response, progression-free survival, overall survival, safety and tolerability.

The study was conducted in collaboration with European Network of Gynaecological Oncological Trial Groups (ENGOT) and Gynecologic Oncology Group (GOG). For more information about the phase 2 innovaTV 204 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov.

About Tisotumab Vedotin

Tisotumab vedotin is an investigational antibody-drug conjugate (ADC) composed of Genmab’s fully human monoclonal antibody specific for tissue factor and Seattle Genetics’ ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody and releases it upon internalization, inducing target cell death. In cancer biology, tissue factor is a protein that can promote tumor growth, angiogenesis and metastases.1 Based on its high expression on many solid tumors and its rapid internalization, tissue factor was selected as a target for an ADC approach. Tisotumab vedotin is being co-developed by Genmab and Seattle Genetics, under an agreement in which the companies share all costs and profits for the product on a 50:50 basis.

Tisotumab vedotin is being evaluated in ongoing clinical trials as monotherapy in a range of solid tumors, including recurrent and/or metastatic cervical cancer, ovarian cancer and in combination with other commonly used therapies in recurrent or metastatic cervical cancer. These trials are evaluating tisotumab vedotin on a weekly or every three weeks dosing schedule.

NantKwest Announces Closing of $90.7 Million Public Offering of Common Stock and Full Exercise of Underwriters’ Option to Purchase Additional Shares

On June 29, 2020 NantKwest, Inc. (Nasdaq: NK), a clinical-stage, natural killer cell-based therapeutics company, reported the closing of its previously announced underwritten public offering of an aggregate of 8,521,500 shares of its common stock (4,811,500 shares at a price to the public of $9.50 per share and 3,710,000 shares at a price of $12.12 per share to NantKwest’s chairman, chief executive officer and principal stockholder, Dr. Patrick Soon-Shiong), which includes 1,111,500 shares sold upon full exercise of the underwriters’ option to purchase additional shares at a public offering price of $9.50 per share, less the underwriting discounts and commissions (Press release, NantKwest, JUN 29, 2020, View Source [SID1234561544]). All of the shares were offered by NantKwest. Including the option exercise, the aggregate gross proceeds of the offering were approximately $90.7 million, before deducting the underwriting discounts and commissions and other offering expenses.

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!

Piper Sandler & Co. acted as the sole book-running manager for the offering. LifeSci Capital acted as co-manager for the offering.

A shelf registration statement on Form S-3 (File No. 333-233434) related to the common stock offered in the public offering described above was filed with the Securities and Exchange Commission (the "SEC") on August 23, 2019 and declared effective by the SEC on September 3, 2019. The offering was made only by means of a prospectus supplement and accompanying prospectus that form a part of the registration statement. A final prospectus supplement and accompanying prospectus related to the offering were filed with the SEC on June 25, 2020 and are available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and accompanying prospectus related to the offering may also be obtained from Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, via telephone at (800) 747-3924 or via email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.