On July 24, 2020 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultra-rare genetic diseases, reported that it will host a conference call on Thursday, July 30, 2020 at 5pm ET to discuss second quarter 2020 financial results and provide a corporate update (Press release, Ultragenyx Pharmaceutical, JUL 24, 2020, https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-host-conference-call-second-quarter-2020-financial [SID1234562322]).

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The live and replayed webcast of the call will be available through the company’s website at View Source To participate in the live call by phone, dial (855) 797-6910 (USA) or (262) 912-6260 (International) and enter the passcode 1808389. The replay of the call will be available for one year.

On July 24, 2020 GlaxoSmithKline plc (LSE/NYSE: GSK) reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the approval of belantamab mafodotin as monotherapy for the treatment of multiple myeloma in adult patients, who have received at least four prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy (Press release, GlaxoSmithKline, JUL 24, 2020, View Source [SID1234562321]).

Dr Axel Hoos, Senior Vice President and Head of Oncology R&D, GSK said: "Today’s positive opinion from the CHMP is an important step in helping patients suffering from relapsed or refractory multiple myeloma who currently have limited options and poor outcomes. If approved, belantamab mafodotin will provide patients and physicians across much of Europe with a first-in-class anti-BCMA treatment option that works differently from other available therapies for this incurable disease."

Belantamab mafodotin was granted PRIME designation in 2017 and the Conditional Marketing Authorisation Application (CMAA) was reviewed under EMA’s accelerated assessment procedure, which is given if the CHMP determines the treatment is of major interest from a public health perspective and represents a therapeutic innovation. The CHMP positive opinion is one of the final steps before marketing authorisation is granted by the European Commission, which has the authority to approve medicines for use throughout the European Union. If approved, belantamab mafodotin will be marketed as BLENREP and will be the second major regulatory milestone for GSK’s oncology portfolio this year.

The CMAA is based on data from the pivotal DREAMM-2 (DRiving Excellence in Approaches to Multiple Myeloma) study including 13-month follow-up data. These data demonstrated that treatment with single-agent belantamab mafodotin, administered as a 2.5 mg/kg dose every three weeks (Q3W), resulted in an overall response rate of 32%. Median duration of response was 11 months and median overall survival was 13.7 months.

The safety and tolerability profile were consistent with previously reported data on belantamab mafodotin. The most commonly reported grade 3 or higher adverse events (occurring in more than 10% of patients) in patients receiving the 2.5 mg/kg dose were keratopathy/microcyst-like epithelial changes (MECs) (46%), thrombocytopenia (22%), anaemia (21%), lymphocyte count decreased (13%) and neutropenia (11%).

Belantamab mafodotin is also under review by the US Food and Drug Administration which granted a priority review for the company’s Biologics License Application (BLA).

About DREAMM-2
DREAMM-2 is an open label study of belantamab mafodotin. Patients in the trial had actively progressing multiple myeloma that had worsened despite current standard of care and were randomised to two arms to receive either 2.5 mg/kg or 3.4 mg/kg belantamab mafodotin Q3W. Overall, patients in DREAMM-2 had more advanced disease, poorer prognosis and performance status and also had a greater number of prior lines of therapy in comparison with patients in DREAMM-1, the first time in human study of belantamab mafodotin.

About multiple myeloma
Multiple myeloma is the third most common blood cancer worldwide and is generally considered treatable, but not curable.[i] Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.[ii]

About B-cell maturation antigen (BCMA)
The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway has been shown to be important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients and BCMA membrane expression is universally detected in myeloma cell lines.ii

About belantamab mafodotin (GSK2857916)
Belantamab mafodotin is an investigational antibody drug conjugate comprising a humanised anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker. The drug linker technology is licensed from Seattle Genetics; monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa.

Belantamab mafodotin is not currently approved for use anywhere in the world.

Trial Name
GSK ID/NCT ID
Status
Design
DREAMM-1
117159/
NCT02064387
Completed
A Phase I Open-label Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma and Other Advanced Hematologic Malignancies Expressing BCMA
DREAMM-2
205678/
NCT03525678
Active, not recruiting
A Phase II Study to Investigate the Efficacy and Safety of Two Doses of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma Who are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed Prior Treatment with an Anti-CD38 Antibody
DREAMM-3
207495/
NCT04162210
Recruiting
A Phase III Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) Compared to Pomalidomide plus low-dose Dexamethasone (Pom/Dex) in Participants with Relapsed/Refractory Multiple Myeloma
DREAMM-4
205207/
NCT03848845
Recruiting
A Phase I/II Single Arm Open-Label Study to Explore Safety and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pembrolizumab in Subjects with Relapsed/Refractory Multiple Myeloma
DREAMM-5
208887/
NCT04126200
Recruiting
A Phase I/II, Randomized, Open-label Platform Study of Belantamab Mafodotin (GSK2857916) with Innovative Combination Anti-Cancer Treatments in Participants with Relapsed/Refractory Multiple Myeloma
DREAMM-6
207497/
NCT03544281
Recruiting
A Phase I/II Randomized Study to Evaluate Safety, Tolerability and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Lenalidomide plus Dexamethasone (Arm A), or in Combination with Bortezomib plus Dexamethasone (Arm B) in Subjects with Relapsed/Refractory Multiple Myeloma
DREAMM-7
207503/
NCT04246047
Recruiting
A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Dexamethasone versus Daratumumab, Bortezomib, and Dexamethasone in Participants with Relapsed/Refractory Multiple Myeloma
DREAMM-8
207499
Planned
A Phase III, Multicentre, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) in Combination with Pomalidomide plus Low-Dose Dexamethasone (BPd) versus Pomalidomide plus Bortezomib and Low-Dose Dexamethasone (PVd) in Participants with Relapsed/Refractory Multiple Myeloma
DREAMM-9
209664/
NCT04091126
Recruiting
A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Lenalidomide and Low-Dose Dexamethasone (VRd) vs. VRd in Participants with Newly Diagnosed Multiple Myeloma who are Ineligible for Transplant
DREAMM-10
207500
Planned
A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with a Novel Agent versus SoC
ISS/GSK Co-Sponsored Study
209418/
NCT03715478
Recruiting
A Phase I/II Dose-escalation and Dose-expansion Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pomalidomide plus Low-dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma Who Have Received Two or More Prior Lines of Therapy That Must Have Included Lenalidomide and a Proteasome Inhibitor

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics, and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

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On July 24, 2020 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, reported it has entered into a definitive securities purchase agreement for the sale of common units and prefunded warrant units, as described below, in a private placement with certain institutional and other accredited investors for gross proceeds to Alpine of approximately $60 million, before deducting placement agent commissions and other offering expenses (Press release, Alpine Immune Sciences, JUL 24, 2020, View Source [SID1234562320]). The private placement is being led by Omega Funds with participation from Avidity Partners, EcoR1 Capital, LLC, Invus Public Equities, L.P., and Samsara BioCapital, among others.

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"The team at Alpine is passionate about solving complex problems in immuno-oncology and autoimmune disease to create innovative and meaningful therapies for patients," said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine Immune Sciences. "Following the announcement of our transformative collaboration with AbbVie, we are entering into a dynamic phase of growth, with two clinical-stage programs in ALPN-101 and ALPN-202, and a third program, ALPN-303, poised to enter the clinic next year. We believe this is just the beginning, and with the support of a distinguished syndicate of new investors, we expect our cash on hand, potential pre-option exercise milestones under our collaboration with AbbVie, and the cash from this private placement to fund our planned operations through 2024."

"The whole Omega Funds’ team is delighted to partner with Mitch and the Alpine team on this transaction," said Otello Stampacchia, Ph.D., Founder and Managing Director of Omega Funds. "The transformative potential of Alpine’s innovative pipeline is impressive. Following the close of this financing, Alpine is well-positioned to advance the development of multiple therapies focused on dramatically improving the standard of care for those living with autoimmune disease and cancer."

Pursuant to the terms of the securities purchase agreement, at the closing of the private placement, Alpine will issue common units representing an aggregate of approximately 5.1 million shares of common stock and warrants to purchase an aggregate of approximately 1.5 million shares of common stock and prefunded warrant units representing prefunded warrants to purchase an aggregate of approximately 0.8 million shares of common stock and warrants to purchase an aggregate of approximately 0.2 million shares of common stock. Each common unit consists of one share of common stock plus a warrant to purchase 0.3 shares of common stock, and each prefunded warrant unit consists of one prefunded warrant to purchase one share of common stock plus a warrant to purchase 0.3 shares of common stock. Both common units and prefunded warrant units will be sold at a price per unit of $10.1175. The warrants will have a per share exercise price of $12.74 and will be exercisable at any time on or after the closing date and will have a 3.5-year term. The prefunded warrants will have a per share exercise price of $0.001 and will be exercisable at any time on or after the closing date. The price of the common units and prefunded warrant units was based in part on the closing price of $10.08 per share of common stock on the Nasdaq Global Market on July 23, 2020.

The private placement is expected to close on or about July 28, 2020, subject to the satisfaction of customary closing conditions. Additional details regarding the private placement will be included in a Form 8-K to be filed by Alpine with the Securities and Exchange Commission ("SEC").

Alpine intends to use the net proceeds to fund the development of its preclinical and clinical pipeline, including ALPN‑101, in systemic lupus erythematosus, ALPN-202, in patients with advanced malignancies, ALPN-303 in B cell-mediated inflammatory diseases, and for general corporate purposes.

Cowen and Company, LLC acted as lead placement agent and Oppenheimer & Co. Inc. acted as a placement agent in the transaction.

The securities being sold in the private placement have not been registered under the Securities Act of 1933, as amended, or state securities laws and may not be offered or sold in the United States absent registration with the SEC or an applicable exemption from such registration requirements. Alpine has agreed to file a registration statement with the SEC covering the resale of the shares of common stock issuable in connection with the private placement and upon exercise of the warrants.

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

On July 24, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) reported that it has initiated a Phase I study of HMPL-306, its novel selective small molecule dual inhibitor of isocitrate dehydrogenase ("IDH") 1 and 2 mutations, in patients with hematological malignancies in China (Press release, Hutchison China MediTech, JUL 24, 2020, https://www.chi-med.com/phase-i-trial-of-idh1-2-dual-inhibitor-in-patients-with-hematological-malignancies-in-china/ [SID1234562315]). The first patient was dosed today.

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This is a multi-center study to evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL‑306 in patients of relapsed or refractory hematological malignancies with an IDH1 and/or IDH2 mutation. The first stage of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of HMPL‑306 to determine the maximum tolerated dose and/or the recommended Phase II dose ("RP2D"). The second stage of the study is a dose expansion phase where three cohorts of patients will receive HMPL‑306 to further evaluate the safety, tolerability, and clinical activity at the RP2D. Additional details may be found at clinicaltrials.gov, using identifier NCT04272957.

HMPL-306 is Chi-Med’s ninth innovative oncology asset discovered in house. Cytoplasmic mutant IDH1 and mitochondrial mutant IDH2 have been known to switch to the other form when targeted by an inhibitor of IDH1 mutant alone or IDH2 mutant alone. By targeting both IDH1 and IDH2 mutations, this drug candidate may provide therapeutic benefits in cancer patients harboring IDH mutations, and may address acquired resistance to IDH inhibition through isoform switching.

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 acute myeloid leukemia ("AML") with approximately 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.[1],[2],[3]

According to the National Cancer Institute (NCI), there will be approximately 20,000 new cases of AML in the U.S. in 2020 and the five-year relative survival rate is 28.7%[4]. Currently, the U.S. Food and Drug Administration (FDA) has approved one drug 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.[5] In China no IDH inhibitor has been approved.

On July 24, 2020 NOXXON Pharma N.V. (Paris:ALNOX) (Euronext Growth Paris: ALNOX), a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported that the Data Safety Monitoring Board (DSMB), in a planned and independent review session, has analyzed safety data from the initial four weeks of treatment of the first patient of the second dose cohort enrolled in the NOX-A12 plus radiotherapy brain cancer trial (Press release, NOXXON, JUL 24, 2020, View Source [SID1234562308]). The DSMB concluded that it is safe and appropriate to continue the recruitment of additional patients according to the study protocol.

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The Phase 1/2 clinical trial is testing three dose regimens of NOX-A12 (200, 400 and 600 mg/week), each combined with external-beam radiotherapy, in newly diagnosed brain cancer patients. The clinical centers participating in the study have now initiated the recruitment of the remaining patients in the second of three escalating dose groups. Once all patients in the second cohort have received a four-weeks treatment of NOX-A12 and radiotherapy, the DSMB will reconvene to determine whether it is safe to proceed to the highest planned dose level of NOX-A12.

"We are encouraged by the additional confirmation of the safety profile of NOX-A12 as we continue moving forward with the increasing dose regimens," commented Aram Mangasarian, CEO of NOXXON. "Following this analysis, the trial can progress as planned, enabling further patients to receive treatment as part of the study protocol. In parallel, the recent capital raises secure our financial runway to well over one year and thereby allow us to remain focused on reaching our goal of obtaining six months of data from the first cohort of patients in October 2020, and from the second and third cohorts at the end of Q1 2021 and mid-2021, respectively."