On November 24, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing oncolytic viruses to target hard-to-treat solid tumors, reported 18-month follow-up data from the randomized phase I/II trial of ONCOS-102 in combination with standard-of-care (SoC) chemotherapy in patients with malignant pleural mesothelioma (MPM) (Press release, Targovax, NOV 24, 2020, View Source [SID1234571637]).

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The study is an open-label, exploratory phase I/II trial adding ONCOS-102 to SoC chemotherapy (pemetrexed/cisplatin) in first- and second- (and later) line treatment of MPM to assess safety, immune activation and efficacy versus SoC only. In total, 31 patients have been included in the trial, with 20 patients in the experimental group receiving the ONCOS-102 and SoC combination (8 randomized in first-line), and 11 patients in the control group receiving SoC only (6 in first-line).

At the 18-month follow-up, more than half of the patients in the first-line ONCOS-102-treated group were still alive, and the mOS was not yet reached. Based on current survival data the mOS will be 18.2 months or longer. For the first-line SoC-only control group, less than half of the patients were alive, and mOS will be 14.2 months or less, which is similar to outcomes from previously reported trials where patients received the same chemotherapy treatment1. An analysis of all the first-line patients, including 3 experimental safety lead-in patients, shows similar results as the randomized first-line patients. The next survival analysis is planned in first half of 2021.

In June, it was reported that ONCOS-102 treatment induces broad and powerful immune activation in MPM, far beyond what is achieved with SoC alone. Importantly, this immune activation is associated with better survival outcomes at the 18-month analysis, indicating that the immunological activity of ONCOS-102 drives the observed clinical benefit.

The powerful immune activation generated by ONCOS-102 builds a strong rationale for combining ONCOS-102 with a checkpoint inhibitor in MPM. This combination could provide further clinical benefits in this indication. Targovax and Merck (known as MSD outside of the USA) are currently reviewing next steps for combining ONCOS-102 and pembrolizumab (Keytruda) in MPM. Recently, the U.S. Food and Drug Administration (FDA) approved the combination of ipilimumab and nivolumab (Yervoy and Opdivo) for the first-line treatment of MPM based on mOS of 18.1 months (Baas 2020), and this is expected to serve as a benchmark for further approvals.

Magnus Jäderberg, Chief Medical Officer of Targovax, said: "We are very pleased that overall survival in first-line patients, is tracking well in the ONCOS-102 treated group. We have already established in the current study that ONCOS-102 drives favorable remodeling of the tumor microenvironment, and we are now starting to see this immune activation translating into the encouraging improved survival outcomes in these 18-month results. This is exactly what we had hoped to see and prepares the way for combining ONCOS-102 with checkpoint inhibition. The immune data suggest to us that survival outcomes in combination with Keytruda may be further improved from the results reported today."

The first results from the trial were announced in January 2020 (see press release here), while immunological data and 12-month survival rate were reported in June 2020 (see press release here) and presented at the SITC (Free SITC Whitepaper) annual meeting in November 2020 (see poster here).

On November 24, 2020 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported a new multi-year drug development partnership with Rappta Therapeutics, a Finland-based biopharmaceutical company, focused on an innovative oncology target (Press release, Evotec, NOV 24, 2020, View Source;announcements/press-releases/p/evotec-and-rappta-therapeutics-enter-discovery-and-development-partnership-focused-on-oncology-target-6002 [SID1234571636]).

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Under the partnership, Evotec will support Rappta’s programme of developing small molecule activators of the enzyme Protein Phosphatase 2A ("PP2A"), which downregulates multiple oncogenic signalling pathways responsible for driving cancer progression. Although PP2A is a key tumour suppressor and has a critical function regulating protein de-phosphorylation and tumour growth, it has to-date been very difficult to target pharmaceutically.

Through its deep understanding of PP2A biology and the use of proprietary technology, Rappta has uniquely defined the PP2A target which has allowed them to come up with a series of first-in-class compounds which glue the three subunits of PP2A together, thus driving PP2A complex reformation and restoring its tumour suppressive function. Evotec and Rappta intend to develop the programme which is currently in the late lead optimisation stage towards IND-enabling studies over the course of their partnership.

The collaboration leverages Evotec’s industry-leading integrated platform for drug discovery and development including Evotec’s oncology expertise coupled with state-of-the-art technologies to maximise probability of success even in fields of cutting-edge and difficult science. Evotec receives undisclosed research funding and is eligible for success-based milestone payments.

Dr Craig Johnstone, Chief Operating Officer of Evotec, commented: "Evotec is pleased to initiate this first collaboration with Rappta Therapeutics supporting their novel and next generation platform targeting PP2A against cancer. Evotec has a long and successful track record in the oncology field, having achieved numerous milestones including multiple pre-clinical candidates and clinical-stage assets together with our partners. We have been thoroughly impressed with the progress that Rappta has made in mapping out the PP2A target and look forward to working with them to continue their success by delivering solutions for patients with unmet medical needs."

Mikko Mannerkoski, the CEO of Rappta Therapeutics, added: "We are excited to be working on building a new platform and a novel class of pharmaceuticals to treat cancer. Rappta has a unique team whose deep understanding of PP2A biochemistry, structural biology, biogenesis, medicinal chemistry, and drug development is further supported by Evotec’s capabilities. This is the perfect combination of expertise to translate these discoveries to the clinic."

On November 23, 2020 Hillstream BioPharma, Inc. ("Hillstream") reported that the FDA granted both the Rare Pediatric Disease Designation (RPD) and Orphan Drug Designation (ODD) to HSB-888 for Osteosarcoma (Press release, Hillstream Biosciences, NOV 23, 2020, View Source [SID1234628149]). Hillstream continues to build an attractive oncology pipeline and expands this oncology pipeline for devastating diseases with this significant milestone achievement for HSB-888. If HSB-888 gains FDA approval by 2023, Hillstream will be given a transferable Priority Review Voucher (PRV) which can be sold to further fund HSB-888 and R&D pipeline.

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Osteosarcoma has been primarily treated with the same frontline chemotherapy for three decades, called MAP, which includes methotrexate, doxorubicin, and cisplatin. The high toxicity of the MAP regimen results in cumulative toxicity which prevents continued use especially in recurrence. HSB-888 could be more efficacious, safer, and a more tolerable therapy which may improve response rates, overall survival, and quality of life. Hillstream is rapidly progressing towards a rapid IND filing process and plans to initiate a clinical trial in pediatric osteosarcoma.

"This acquisition significantly expands our oncology business with a late stage product and diversifies our oncology portfolio" stated Randy Milby, founder and chief executive officer of Hillstream. "The Rare Pediatric Disease Designation and Orphan Drug Designation for the treatment of osteosarcoma highlights the significant need for patients with this devastating disease. With the clinical data currently available, we anticipate a rapid progression toward an IND and initiation of Phase 1b/2a trials. We look forward to sharing our progress about these and future milestones with current and potential shareholders."

In addition, Hillstream continues progressing its pre-clinical pipeline of assets, including HSB-1216 for the treatment of small cell lung cancer. HBS-1216 is a potent cancer stem cell inhibitor. This combined portfolio enables Hillstream to have additional capability to address unmet needs in multiple, high, unmet-need orphan tumors.

About Pediatric Osteosarcoma

Osteosarcoma remains the most common primary pediatric bone malignancy mostly occurring in adolescents for which treatment has remained essentially unchanged for more than three decades. Osteosarcoma is a highly aggressive tumor with metastatic disease either at diagnosis or at the time of recurrence portending a poor prognosis with five-year survival rate survival below 30%. Osteosarcoma is found in about one thousand people with about half diagnosed in adolescents in the United States each year, most often during the growth spurt of the teen years.

About Rare Pediatric Disease Designation and Orphan Drug Designation

The U.S. Food and Drug Administration (FDA) Office of Orphan Products Development granted Orphan Drug Designation (ODD) to HSB-888 for the treatment of pediatric osteosarcoma, a rare pediatric cancer. The FDA grants ODD to therapies targeting conditions that affect fewer than 200,000 people in the U.S. The designation provides seven-year market exclusivity, increased engagement, and assistance from the FDA, tax credits for certain research, research grants, and a waiver of the New Drug Application user fee. HSB-888 also has Rare Pediatric Disease Designation for osteosarcoma. The FDA grants Rare Pediatric Disease Designation for serious and life-threatening diseases that primarily affect children ages 18 years or younger and fewer than 200,000 people in the U.S. If Hillstream’s new drug application for osteosarcoma is approved, Hillstream may receive a priority review voucher from the FDA, which can be redeemed to obtain priority review for any subsequent marketing application or may be sold to another company for their programs.

On November 23, 2022 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics designed to selectively engage and modulate targeted T cells within the patient’s body, reported that it participated in a pre-recorded fireside chat as part of the Piper Sandler 32nd Annual Virtual Healthcare Conference, being held on December 1-3, 2020 (Press release, Cue Biopharma, NOV 23, 2020, View Source [SID1234608287]).

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The pre-recorded presentation will be available to participants during the conference and on the Events page of the Investors & Media section of the Company’s website www.cuebiopharma.com beginning today, November 23, 2020 at 10:00 a.m. EST. An archived version of the recording will be accessible for 90 days following the event.

On November 23, 2020 Merck (NYSE: MRK), known as MSD outside the United States and Canada, and OncoImmune, a privately-held, clinical-stage biopharmaceutical company, reported that the companies have entered into a definitive agreement pursuant to which Merck, through a subsidiary, will acquire all outstanding shares of OncoImmune for an upfront payment of $425 million in cash (Press release, Merck & Co, NOV 23, 2020, View Source [SID1234586359]). In addition, OncoImmune shareholders will be eligible to receive sales-based payments and payments contingent on the successful achievement of certain regulatory milestones. OncoImmune recently announced positive top-line findings from an interim efficacy analysis of a Phase 3 study evaluating its lead therapeutic candidate CD24Fc for the treatment of patients with severe and critical COVID-19.

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"Meaningful new therapeutic options are desperately needed for possibly millions of people around the world who will develop severe or critical COVID-19 disease," said Dr. Roger M. Perlmutter, President Merck Research Laboratories. "Recent clinical investigations support the view that CD24Fc may provide benefit beyond standard of care therapy for COVID-19 patients requiring oxygen support, and hence will represent an important addition to the Merck pipeline of investigational medicines and vaccines designed to address the COVID-19 pandemic."

Interim analysis of data from 203 participants (75% of the planned enrollment) reported by OncoImmune indicated that patients with severe or critical COVID-19 treated with a single dose of CD24Fc showed a 60% higher probability of improvement in clinical status, as defined by the protocol, compared to placebo. The risk of death or respiratory failure was reduced by more than 50%. Detailed results will be submitted for publication in a peer-reviewed medical journal.

"Outstanding work by the OncoImmune team has provided compelling evidence regarding the use of CD24Fc in patients with severe and critical COVID-19 in our Phase 3 Trial," said Yang Liu, PhD, Co-founder and Chief Executive Officer of OncoImmune. "We look forward to working with the scientists and manufacturing engineers at Merck as well as regulators as we seek to accelerate the global development of this potentially important therapy."

Under the agreement, prior to the completion of the acquisition, OncoImmune will spin-out certain rights and assets unrelated to the CD24Fc program to a new entity to be owned by the existing shareholders of OncoImmune. In connection with the closing of the acquisition, Merck will invest $50 million, and become a minority shareholder, in the new entity.

The closing of the acquisition, which is subject to approval under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions, is expected before the end of 2020.

OncoImmune was represented by Goodwin Procter LLP as legal advisor and Guggenheim Securities as financial advisor.

About SAC-COVID Phase 3 Trial

The SAC-COVID Phase 3 clinical trial (NCT04317040) is a randomized, double blind, placebo-controlled trial designed to evaluate the safety and efficacy of CD24Fc in hospitalized patients with COVID-19 requiring oxygen support, including those requiring supplemental oxygen, high flow oxygen, and mechanical ventilation. Participants were randomly assigned into two arms receiving either standard of care plus a single dose of CD24Fc via an intravenous infusion on Day 1 or standard of care plus placebo on Day 1. The multi-center trial was initiated in April 2020 and had enrolled 243 patients when the trial was closed to enrollment in September 2020.

About CD24Fc

OncoImmune’s lead product is CD24Fc, a first-in-class recombinant fusion protein that targets the innate immune system. Prior to the Phase 3 clinical trial for COVID-19 patients, CD24Fc has been studied for safety in healthy volunteers and in Phase 2 clinical trials for the prevention of graft versus host disease (GVHD) following hematopoietic stem cell transplantation in patients with leukemia. A pivotal Phase 3 clinical trial (NCT04095858) for prophylaxis of GVHD has been initiated nationwide.

About Merck’s ongoing Commitment to COVID-19

Merck has been committed to developing an effective response to COVID-19 since the early stage of the pandemic and is exploring multiple paths to advance the understanding of SARS-CoV-2 infection. In collaboration with Ridgeback Biotherapeutics, Merck is evaluating molnupiravir, an investigational orally available anti-viral candidate, in two Phase 2/3 trials, for the treatment of patients with COVID-19 in both the outpatient and inpatient settings.The company is also conducting clinical trials to evaluate two SARS-CoV-2/COVID-19 vaccine candidates: V590, being developed through a collaboration with IAVI, which utilizes a recombinant vesicular stomatitis vector, and V591 which uses a measles virus vector-based platform.