On December 2, 2021 GlaxoSmithKline plc and the University of Oxford reported a major five-year collaboration to establish the Oxford-GSK Institute of Molecular and Computational Medicine (Press release, GlaxoSmithKline, DEC 2, 2021, View Source [SID1234596388]). The new Institute, which will be based at the University of Oxford, aims to improve the success and speed of research and development of new medicines, building on insights from human genetics and using advanced technologies such as functional genomics and machine learning.

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Genetic evidence has already been shown to double success rates in clinical studies of new treatments, and the digitisation of human biology has the potential to improve drug discovery by more closely linking genes to patients. The new Institute aims to build on this scientific progress and improve how diseases are understood by drawing on recent advances in pathology, including how to measure changes on a cellular, protein, or tissue level.

Backed by £30 million from GSK, the Institute is intended to pioneer further improvements in how new medicines are discovered and developed. For example, scientists from GSK and Oxford will help prioritise those early R&D programmes most likely to succeed and match them to patients most likely to respond.

The Institute will evaluate and integrate new approaches in genetics, proteomics and digital pathology to understand detailed patterns of disease which vary amongst individuals. The initial focus of research will be on neurological diseases, such as Alzheimer’s and Parkinson’s Disease.

Prime Minister Boris Johnson said: "We saw first-hand during the pandemic how the ingenuity and pioneering spirit of UK scientists and the R&D sector saved thousands of lives, with the rapid development and delivery of medicines and vaccines around the world.

"I am delighted to see that GSK and the University of Oxford are today taking further steps to deepen our understanding of some of the most complex diseases, such as Parkinson’s. Together they will harness the power of scientific collaboration to progress cutting-edge technologies and accelerate drug discovery – helping to cement the UK’s role as a life sciences superpower."

Emma Walmsley, Chief Executive Officer, GSK said: "We are delighted to be joining with the University of Oxford in this new collaboration. By combining the strengths of our two scientific organisations and harnessing advanced technologies, the Oxford-GSK Institute exemplifies the UK’s track-record and continued ambition in life sciences. Together, our aim is to improve drug discovery and development to help bring new and better medicines for patients."

Professor Louise Richardson, Vice-Chancellor of the University of Oxford, said: "On behalf of colleagues across Oxford I would like to say how delighted we are by this new initiative with GSK. The Institute will create a unique partnership with staff from the university’s medical school and GSK working side-by-side to research and develop treatments for some of the most difficult to treat diseases. In addition, the Institute, in keeping with our educational mission, will provide training and build capacity in Britain’s academic and bioscience sectors."

The genetic and genomic revolution of the past decade has amassed vast datasets of promising targets for medicine discovery. These datasets can be combined with functional genomics to provide deep understanding of disease at a molecular level.

By harnessing this understanding, as well as the power of machine learning, the Institute will uncover new indicators and predictors of disease and use them to accelerate the most promising areas for drug discovery. This is particularly important for GSK as it prioritises the large number of genetically informed drug targets generated from its collaborations with organisations, such as 23andMe and UK Biobank. The Institute will also aim to provide new measurements to establish proof of concept for potential medicines earlier in the R&D process, by better identifying the most appropriate patients to enrol in clinical trials, thus accelerating drug development timelines.

GSK and Oxford bring complementary capabilities and expertise into the Institute. GSK has leading capabilities in human genetics and functional genomics, and an in-house artificial intelligence and machine learning function, including its AI hub in central London. The University of Oxford has similar expertise but together they will be using patient, molecular information and state-of-the-art platforms to pinpoint the GSK targets that are most likely to succeed and be developed into safe, effective, disease mechanism-based medicines.

Diseases driven by neuro-immunological mechanisms including Alzheimer’s, Parkinson’s, Multiple Sclerosis (MS), Frontal Temporal Dementia, Amyotrophic Lateral Sclerosis (ALS) and Pain will be within the initial scope of the Institute. GSK has a rich pipeline of genetically informed targets and clinical projects in these areas.

The Institute will recruit a number of new research groups, in addition to drawing upon existing expertise from both GSK and Oxford. Five GSK/Oxford fellowships will be provided for early to mid-career researchers to establish themselves as Principal Investigators researching areas aligned with the Institute’s aims and objectives.

The Institute will have its base in the Nuffield Department of Medicine, and be closely associated with colleagues from across departments, including the University’s Wellcome Centre for Human Genetics and Big Data Institute. GSK and Oxford are in active discussions regarding the nature of the first projects which are anticipated to start in the second half of 2022 and will use the latest laboratory and data science platforms and approaches. A completely new way of collaborating will be established where research teams will have both GSK and University members, including secondments between both institutions.

The Directors of the Institute will be Professor John Todd, Director of the Wellcome Centre for Human Genetics and Dr Tony Wood, SVP, Medicinal Science and Technology at GSK.

On December 2, 2021 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported that early preliminary data from an investigator-initiated Phase 2 open label trial of rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC) were presented at the Austrian Society of Dermatology and Venerology Annual Conference 2021, which took place from November 25 – 27, 2021 (Press release, Onconova, DEC 2, 2021, View Source [SID1234596407]).

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RDEB is an ultra-rare condition caused by a lack of type VII collagen protein expression. Type VII collagen protein is responsible for anchoring the skin’s inner layer to its outer layer, and its absence leads to extreme skin fragility and chronic wound formation in RDEB patients. Over time, many of these patients develop squamous cell carcinomas (SCCs) that typically arise in areas of chronic skin wounding and inflammation. Preclinical investigations demonstrated overexpression of polo like kinase 1 (PLK1) in RDEB-associated SCC tumor cells. These tumors show a highly aggressive, early metastasizing course, making them the primary cause of death for these patients, with a cumulative risk of death of 70% and 78.7% by age 45 and 55, respectively1,2. These neoplasms show limited response rates of mostly short duration to conventional chemo- and radiotherapy as well as targeted therapy with epidermal growth factor and tyrosine kinase inhibitors1,3.

Data from the recent presentation are from a 24-year-old RDEB patient with a history of multiple, unresectable SCCs that were unresponsive to prior treatments including cemiplimab. Results showed that intravenously administered rigosertib had an acceptable safety profile and that the patient experienced sustained clinical and histological remission of all target lesions without signs of metastatic disease following 13 treatment cycles. The patient remains on study and the trial remains ongoing. The enrollment of additional patients is anticipated at sites in Salzburg, Austria; London, UK; and Philadelphia, Pennsylvania.

"Though the trial’s currently available data are from only a single patient, they represent an exciting and powerful finding that warrants further study," said Andrew South Ph.D., Associate Professor, Department of Dermatology & Cutaneous Biology, Thomas Jefferson University. "RDEB-associated SCC is an indication with an extremely high unmet medical need, as it is invariably fatal with treatment options that have so far yielded disappointing results. The data generated in preclinical models suggesting rigosertib’s robust activity against PLK1 have now been confirmed in the clinic and suggest that rigosertib may play a role in other more common cancers driven by PLK1."

The physicians caring for the patient, Dr. Bauer, Principal Investigator, and Dr. Laimer, Sponsor Medical Expert of the trial, added in a joint statement, "To see a complete response in a patient that has failed multiple prior therapies is highly encouraging and, together with preclinical data, suggests that rigosertib’s ability to inhibit PLK1 may position it as a novel treatment option that can significantly improve upon the current standard-of-care. We look forward to the further evaluation of this hypothesis through the continued advancement of the trial."

A copy of the poster, titled "Rigosertib for locally advanced/metastatic EB-associated SCC," is available on the "Scientific Presentations" section of the Onconova website.

References

Mellerio et al. Br J Dermatol. 2016 Jan; 174(1):56-67. doi: 10.1111/bjd.14104.
Fine et al. J Am Acad Dermatol. 2009 Feb; 60(2):203-11. doi: 10.1016/j.jaad.2008.09.035.
Stratigos et al. Eur J Cancer. 2020 Mar;128:83-102. doi: 10.1016/j.ejca.2020.01.008.

On December 2, 2021 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported the pricing of an underwritten public offering of 11,636,364 shares of its common stock at a price of $6.60 per share, before underwriting discounts and commissions, and to certain investors in lieu of common stock, pre-funded warrants to purchase up to an aggregate of 27,363,636 shares of its common stock at a price of $6.59, which represents the per share public offering price for the common stock less the $0.01 per share exercise price for each such pre-funded warrant (Press release, ImmunoGen, DEC 2, 2021, View Source [SID1234596389]). The offering is expected to close on or about December 6, 2021, subject to satisfaction of customary closing conditions. ImmunoGen also granted the underwriters a 30-day option to purchase up to an additional 5,850,000 shares of its common stock at the public offering price, less underwriting discounts and commissions. All of the shares of common stock and pre-funded warrants in the offering are to be sold by ImmunoGen.

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ImmunoGen anticipates the total gross proceeds from the offering (before deducting the underwriting discounts and estimated offering expenses) will be $257.1 million, excluding any exercise of the underwriters’ option to purchase additional shares.

ImmunoGen intends to use the net proceeds of the offering to fund its operations, including, but not limited to, commercialization activities, clinical trial activities, supply of drug product, business development activities, capital expenditures, and working capital.

Jefferies, Cowen, and Guggenheim Securities are acting as joint book-running managers for the proposed offering. Canaccord Genuity is acting as lead manager for the proposed offering.

The securities described above are being offered by ImmunoGen pursuant to a shelf registration statement that was previously filed with the Securities and Exchange Commission (SEC) and became effective upon filing. This press release does not constitute an offer to sell or a solicitation of an offer to buy the securities in this offering, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation, or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. A preliminary prospectus supplement and accompanying prospectus relating to the offering was filed with the SEC and is available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to this offering may be obtained by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by e-mail at [email protected] or by telephone at (877) 821-7388; Cowen and Company, LLC c/o Broadridge Financial Solutions, Attention: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY,11717, by email at [email protected] or by telephone at (833) 297-2926; or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, or by email at [email protected] or by telephone at (212) 518-9544.

On December 2, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported the publication of the abstract highlighting interim data, as of a July 14, 2021 cutoff, from the phase 1/2 trial of bispecific antibody MCLA-145 in patients with solid tumors (Press release, Merus, DEC 2, 2021, View Source [SID1234596408]). The e-poster will be presented at the ESMO (Free ESMO Whitepaper) Immuno-Oncology (ESMO IO) Congress 2021 being held December 8-11, 2021 in Geneva, Switzerland.

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Presentation Details:

Title: Phase I Dose Escalation Study of MCLA-145, a Bispecific Antibody Targeting CD137 and PD-L1 in Solid Tumors
Poster #: 136P

The e-poster will be available on the virtual platform, in the e-poster section as of Monday, December 6 at 6:00 am ET and on-site at the e-Poster stations starting on Wednesday, December 8. The poster will also be available on the Merus website.

The phase 1, open-label, single-agent clinical trial of MCLA-145 is ongoing. The trial consists of a dose escalation phase, followed by a planned dose expansion phase. MCLA-145 is the first drug candidate co-developed under Merus’ global collaboration and license agreement with Incyte, which permits the development and commercialization of up to 11 bispecific and monospecific antibodies from the Merus Biclonics platform. Merus retains full rights to develop and commercialize MCLA-145, if approved, in the United States; and Incyte holds full rights to develop and commercialize MCLA-145 outside the United States.

About MCLA-145
Discovered through an unbiased functional screening of multiple immunomodulatory target combinations, MCLA-145 is a Biclonics T-cell agonist that binds with high affinity and specificity to human PD-L1 and CD137 in preclinical models. The unique immunostimulatory profile of MCLA-145 derives from the potential to potently activate immune effector cells in the context of the tumor microenvironment while simultaneously blocking inhibitory signals in the same immune cell population.

On December 2, 2021 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel LAG-3 related immunotherapy treatments for cancer and autoimmune disease, reported the first five patients have been treated in the INSIGHT-003 study (Press release, Immutep, DEC 2, 2021, View Source [SID1234596428]).

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No additional safety signals have been observed in the study which is the first time a triple combination therapy consisting of eftilagimod alpha ("efti") and an existing approved standard of care combination of chemotherapy (carboplatin) and an anti-PD-1 therapy has been administered.

Lead investigator, Prof. Dr. Salah-Eddin Al-Batran of the Institute of Clinical Cancer Research IKF said: "The INSIGHT-003 study has commenced well. We are very pleased with the safety of the triple combination so far and all patients are still participating in the study. This is important as it is the first time patients have received a triple combination therapy with efti. Patient recruitment is advancing in line with our projections."

INSIGHT-003 is evaluating a triple combination therapy consisting of efti in conjunction with an existing approved standard of care combination of chemotherapy and anti-PD-1 therapy. The study will continue to recruit up to 20 patients with various solid tumours and additional results are expected in calendar year 2022.

About INSIGHT-003

INSIGHT-003 is an investigator-initiated study conducted by the Institute of Clinical Cancer Research IKF at Krankenhaus Nordwest in Frankfurt. It is being run as the third arm (Stratum C) of the ongoing Phase I INSIGHT trial with Prof. Dr. Salah-Eddin Al-Batran as lead investigator. The study is evaluating a triple combination therapy consisting of efti in conjunction with an existing approved standard of care combination of chemotherapy (carboplatin) and anti-PD-1 therapy.

Up to 20 patients with solid tumours will be recruited to participate in the trial. Patients will receive 30 mg subcutaneous doses of efti every two weeks in conjunction with standard of care chemotherapy plus anti-PD-1 therapy. The trial will assess the safety, tolerability and initial efficacy of the combination.