On November 8, 2021BioXcel Therapeutics reported that it raised $60 million in an initial public offering a few years back, it said it would pour part of the proceeds into developing talabostat, a drug that failed a phase 3 trial in pancreatic cancer in 2007 (Press release, BioXcel Therapeutics, NOV 8, 2021, View Source [SID1234595336]). Now, BioXcel, along with collaborators at Georgetown University, has preclinical data suggesting the drug may boost the benefits of immunotherapy in this tough-to-treat cancer.

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Georgetown researchers tested talabostat (also known as BXCL701) alone and alongside a treatment that inhibits the immune checkpoint PD-1 in mouse models of pancreatic cancer. Both treatments slowed tumor growth, and the combination significantly increased the recruitment of cancer-fighting immune cells, the researchers reported in the Journal for ImmunoTherapy of Cancer.

Talabostat works by inhibiting the protein dipeptidyl peptidase (DPP). Knowing that earlier studies had suggested the drug might improve immunotherapy, the Georgetown researchers wanted to see what would happen if they combined it with PD-1 inhibition. Checkpoint blockade has worked in many cancer types but has so far not panned out in pancreatic cancer.

They discovered that talabostat ramped up the infiltration of T cells and natural killer (NK) cells into the pancreatic tumor environment. Combining the drug with anti-PD-1 therapy not only slowed tumor growth and boosted immune activity, it also created "immune memory" in 10 out of 13 mice that had been cured by the initial therapy, allowing them to clear some tumors after they were re-exposed to pancreatic cancer months later.

The researchers believe the key to the combination’s effectiveness rested in the recruitment of NK cells, which combat cancer in two ways: They kill cancer cells directly, and they release "signaling molecules" that regulate other aspects of the immune system in ways that control tumor growth, they explained in a statement.

To back up their hunch, they studied real-world data in the National Institutes of Health’s Cancer Genome Atlas and found that increased levels of NK cells in human pancreatic tumors correlated with longer survival, the team reported.

RELATED: AACR (Free AACR Whitepaper): Attacking pancreatic cancer by thwarting its survival strategies

NK cells are of great interest to several research groups and biotechs that are searching for new approaches to treating solid tumors. Fate Therapeutics, for example, is developing an NK cell therapy that in preclinical studies killed cancer cells—including pancreatic tumor cells—when combined with anti-PD-1 therapy. The investigational product, FT500, is now in phase 1 testing in advanced solid tumors.

Other combinations designed to boost the immune response are under investigation in pancreatic cancer. Last year at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) conference, a University of Minnesota team reported that combining a PD-L1 inhibitor with a CD40 blocker in mouse models of pancreatic cancer eliminated tumors in 60% of the animals. Apexigen is testing its CD40-targeted drug in combination with Bristol Myers Squibb’s PD-1 blocker Opdivo and other therapies in pancreatic cancer and reported survival benefits over the standard of care earlier this year.

As for BioXcel, it is currently testing talabostat in combination with Merck’s blockbuster PD-1 inhibitor Keytruda in metastatic castration-resistant prostate cancer and some tumors that are resistant to immune checkpoint inhibitors.

The Georgetown researchers said they’re planning to conduct additional animal trials to better understand the mechanism of action of the talabostat-anti-PD-1 combination in pancreatic tumors. From there, they hope to design a clinical trial, they said.

On November 8, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, and Blackstone Life Sciences reported that the two companies have entered into a strategic collaboration and financing agreement under which funds managed by Blackstone (NYSE: BX) will provide up to $250 million in equity and product financing to support Autolus’ advancement of its CD19 CAR T cell investigational therapy product candidate, obecabtagene autoleucel (obe-cel), as well as next generation product therapies of obe-cel in B-cell malignancies (Press release, Blackstone Life Sciences, NOV 8, 2021, View Source [SID1234595327]).

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As part of this $250 million transaction, Blackstone is committing to invest $150 million in product financing to support obe-cel development and commercialization, with $50 million payable upon closing of the transaction and the remainder payable based on certain development and regulatory achievements. Blackstone has also agreed to purchase $100 million of Autolus’ American Depositary Shares (ADS) in a private placement, which is subject to customary closing conditions. In connection with the collaboration, Blackstone received the right to nominate a member to Autolus’ board of directors.

The transaction continues Blackstone’s commitment to the UK economy which has seen the firm invest more than $18 billion across 44 investments headquartered in UK. These investments support more than 27,000 direct jobs and help make Blackstone the UK’s biggest foreign investor over the past 10 years.

"Autolus is a world-class company with an innovative platform and the potential to deliver best-in-class, lifesaving treatments to patients suffering from cancer," said Dr. Nicholas Galakatos, Global Head of Blackstone Life Sciences. "Our investment in these next generation cell therapies exemplify our conviction in the quality and promise of the life sciences sector in the UK. We look forward to building on this investment in the years to come."

"We welcome Blackstone Life Sciences to join our drive to change the outlook for leukemia and lymphoma patients, notably those with acute lymphoblastic leukemia. Blackstone’s investment and expertise will support the development and preparation for commercialization of obe-cel and put the program and the Company on a strong financial footing as we are approaching the read-out from the potentially pivotal FELIX clinical trial during the course of 2022," said Dr. Christian Itin, Chief Executive Officer of Autolus.

"We are excited to collaborate with Autolus in support of their innovative platform pursuing safer, more durable, therapies with the potential to be lifesaving options for patients with ALL and beyond. We see a significant opportunity to improve the outlook for cancer patients who are facing a devastating course of their disease," said Nicholas Simon, Senior Managing Director of Blackstone Life Sciences. "This investment continues to build on our conviction in not just innovative cell and gene therapies, but also supporting innovation in the United Kingdom and Europe broadly."

UK Science Minister George Freeman said: "This is another vote of confidence in the quality of life science in the UK, reinforcing our reputation as a world leader in discovering new cures for currently untreatable diseases like Autolus’ T cell therapy drugs for leukemia. Big investments like these give real hope to those suffering from diseases like leukemia – and create high skill jobs & opportunities in the development and manufacturing of treatments to help develop and boost our life science clusters all around the UK."

Autolus recently announced plans to build a dedicated manufacturing facility in Stevenage, UK to help secure global commercial launch capacity for obe-cel with a 70,000 square foot building. The ground-breaking ceremony for this new facility is due to be held today, with building works commencing imminently.

Moelis & Company LLC acted as financial advisor. Cooley LLP and Cooley (UK) LLP acted as legal advisor to Autolus, and Goodwin Procter LLP acted as legal advisor to Blackstone.

About the Transaction

The strategic financing collaboration by Autolus and Blackstone Life Sciences is expected to support the development and preparation for commercialization of Autolus’ product candidate, obe-cel. As part of this $250 million transaction, Blackstone is committing to invest an aggregate of $150 million in product financing to support Autolus’ development and potential commercialization of obe-cel, with $50 million payable upon closing of the transaction and the remainder (up to $100 million) payable based on certain development and regulatory achievements. In return for this strategic investment, Autolus has agreed to pay Blackstone a capped single digit royalty plus milestone payments based on net sales of obe‐cel. In addition, Blackstone will receive a warrant to purchase up to $24 million worth of Autolus ADSs at an exercise price premium to market. Blackstone has also agreed to make a $100 million equity investment in Autolus which is expected to close on or about November 12, 2021, subject to customary closing conditions. In connection with the collaboration, Blackstone received the right to nominate a member to Autolus’ board of directors.

On November 8, 2021 Delcath Systems, Inc. (Nasdaq: DCTH ), an interventional oncology company focused on the treatment of rare primary and metastatic cancers of the liver, reported it will participate in an upcoming virtual investor conference (Press release, Delcath Systems, NOV 8, 2021, View Source [SID1234595227]):

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On November 8, 2021 Race Oncology Limited ("Race") reported that it has entered into a strategic collaborative research agreement with the University of Wollongong (UOW) to undertake preclinical evaluation of new Zantrene formulations designed by Race (Press release, Race Oncology, NOV 8, 2021, View Source [SID1234595209]). This collaboration is expected to provide significant value to the company by expanding the market potential of Zantrene for new and existing cancer indications. All IP generated will be owned by Race royalty free.

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"This is an exciting and valuable collaboration for Race as we develop new Zantrene formulations and expand our pipeline. We are very much looking forward to working with Professor Ranson on this important program and building on the clinical lead we have in the m6A RNA methylation field via our FTO targeted drug Zantrene."

Chief Scientific Officer, Dr Daniel Tillett
Improved Formulations of Zantrene
Current administration of Zantrene requires the use of a central venous catheter in a hospital setting. While this is standard practice for the delivery of many chemotherapy drugs, longer-acting and more patient-friendly routes of administration are desirable if the full market potential of Zantrene is to be achieved.

Through a series of internal and collaborative programs, Race has designed and is developing several new proprietary Zantrene formulations that offer the potential for long-acting peripheral IV administration in an outpatient setting. Additional programs have identified a number of formulation approaches that could allow Zantrene to be delivered orally.The UOW collaboration provides Race with access to the lab, instrumental capabilities and expertise required to rapidly advance formulation development at lower cost and greater speed, while generating and capturing new patentable IP.

"As our preclinical programs mature, having the capacity to rapidly evaluate and subtly optimise formulations is an essential requirement in pharmaceutical development. I worked extensively on cancer drug development projects with Prof. Ranson while at UOW and a big part of our success can be attributed to an outstanding young PhD student and later postdoc with us, Dr Benjamin Buckley. It is fantastic to now have Ben’s expertise on the Race team and to be working together again alongside Prof Ranson to develop and expand our leading asset Zantrene."

Principal Scientist, Professor Michael Kelso
Team
These programs are to be led by Professor Marie Ranson in collaboration with Race’s Principal Scientist, Professor Michael Kelso. Prof Ranson is an esteemed cancer biologist with extensive experience in drug development and formulation. She has joint appointments at the Illawarra Health and Medical Research Institute and Molecular Horizons Institute at the University Wollongong. Professor Ranson has published more than 110 peer-reviewed scientific papers in the area of oncology and drug development, holds several patents and has attracted over $20 million in research and industry funding.

"As a scientist who spends most of my time investigating basic biological processes, the opportunity to work with Race to develop new drug formulations that could translate into tangible benefits for cancer patients is extremely exciting. Zantrene shows immense promise as an effective new cancer drug and I am delighted to be working with my former UOW colleagues, Prof Kelso and Dr Buckley, in this collaboration with Race".

Professor Ranson
To support this program, Race has recruited a new Senior Scientist, Dr Benjamin Buckley, to perform work in Prof. Ranson’s lab. Dr Buckley brings over 8 years of doctoral training and postdoctoral experience in drug discovery and development to the Race team.

"I’m thrilled to be joining the team at Race and advancing formulations that can further realise the potential of Zantrene. Working in the Ranson Lab and leveraging the state-of-the-art facilities, expertise and instrumentation available at both UOW and the Illawarra Health and Medical Research Institute adds considerable value to Race’s ‘Three Pillar’ strategy. Together with Profs Ranson, Kelso and the Race team, I very much look forward to capitalising on Zantrene’s significant first-mover advantage and showing the true clinical value of targeting FTO in difficult-to-treat cancers".

Dr Ben Buckley
This collaboration is to start immediately with results to be reported over the coming 12 months. While the contract value is not material in dollar terms, it is significant in that it transforms our R&D capability, so we can optimise and enhance Zantrene formulations and their utility in additional patient settings.

On November 8, 2021 Celcuity Inc. (Nasdaq: CELC), a clinical-stage biotechnology company pursuing an integrated therapeutic and companion diagnostic strategy for treating patients with cancer, reported financial results for the third quarter ended September 30, 2021 and summarized recent business progress (Press release, Celcuity, NOV 8, 2021, View Source [SID1234595207]).

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"We made great progress advancing our gedatolisib program this past quarter. We initiated preparation for a Phase 3 clinical trial evaluating gedatolisib in combination with Ibrance and Faslodex in patients with ER+/HER2- advanced or metastatic breast cancer that we expect to activate in the first half of 2022," said Brian Sullivan, CEO and co-founder of Celcuity. "Site identification and feasibility activities are underway. We are excited to have the opportunity to present updated results from our Phase 1b clinical trial in patients with ER+/HER2- advanced breast cancer at the San Antonio Breast Cancer Symposium in December. Finally, we are pleased to have entered into another clinical trial collaboration to evaluate CELsignia selected patients with advanced breast cancer. The collaboration with University of Rochester Wilmot Cancer Center and Puma represents an important opportunity to identify a potential new treatment for patients with breast cancer that has metastasized to the brain."

Third Quarter 2021 Business Highlights and Other Recent Developments

Completed transfer of regulatory, clinical trial, and safety reporting responsibilities for gedatolisib from Pfizer to Celcuity ahead of schedule.

Updated data from Celcuity’s ongoing Phase 1b clinical trial for patients with ER+/HER2- advanced breast cancer will be presented at the San Antonio Breast Cancer Symposium during a Spotlight Poster Discussion Session on December 10, 2021. Rachel M. Layman, MD, an oncologist at the University of Texas MD Anderson Cancer Center who was a principal investigator for the clinical trial, will be the presenting author.

Celcuity entered into a clinical trial collaboration agreement with the University of Rochester Wilmot Cancer Center and Puma Biotechnology in October 2021. This single arm Phase 2 trial will evaluate the efficacy and safety of Puma’s pan-HER inhibitor, NERLYNX (neratinib), and capecitabine, a chemotherapy, in patients selected with Celcuity’s CELsignia HER2 Activity Test who have metastatic HER2-negative breast cancer that has progressed on prior treatments. Based on estimates of patient enrollment rates, Celcuity expects to obtain interim results 12 to 15 months after initiation of the trial followed by the final results 12 to 15 months later. Enrollment is planned to begin by mid-2022.

Enrollment in the FACT-1 and FACT-2 trials that are evaluating CELsignia selected patients who have early-stage ER+/HER2- breast cancer was negatively impacted by COVID-19 related delays during the third quarter. Hospitalizations of patients with COVID-19 increased dramatically during this period which led hospitals to reduce clinical trial related activities. Interim results are now expected to be available in the second half of 2022.

Third Quarter 2021 Financial Results

Unless otherwise stated, all comparisons are for the third quarter ended September 30, 2021, compared to the third quarter ended September 30, 2020. The following discussion should be read in conjunction with our unaudited condensed consolidated financial statements and related notes on Form 10-Q for the third quarter ended September 30, 2021.

Total operating expenses were $5.6 million for the third quarter of 2021, compared to $2.5 million for the third quarter of 2020.

Research and development (R&D) expenses were $5.0 million for the third quarter of 2021, compared to $2.0 million for the third quarter of 2020. The increase in R&D expenses during the third quarter of 2021 compared to the prior year primarily resulted from costs associated with the development of gedatolisib. Employee related expenses, including consulting fees, accounted for $1.1 million of the increase. The remaining increase of $1.9 million in expenses is related to clinical trials, patent legal fees, and costs associated with the transfer of the gedatolisib-related activities from Pfizer to Celcuity.

General and administrative (G&A) expenses were $0.6 million for the third quarter of 2021, compared to $0.5 million for the third quarter of 2020. The increase in the third quarter of 2021 arose primarily from non-cash stock-based compensation.

Net loss for the third quarter of 2021 was $6.0 million, or $0.41 loss per share, compared to a net loss of $2.5 million for the third quarter of 2020, or $0.24 loss per share. The Non-GAAP adjusted net loss for the third quarter of 2021 was $5.1 million compared to a non-GAAP adjusted net loss of $2.0 million for the third quarter of 2020. Non-GAAP adjusted net loss excludes stock-based compensation expense, issuance of common stock and non-cash interest. Because these items have no impact on Celcuity’s cash position, management believes non-GAAP adjusted net loss better enables Celcuity to focus on cash used in operations. For a reconciliation of financial measures calculated in accordance with generally accepted accounting principles (GAAP) in the United States to non-GAAP financial measures, please see the financial tables at the end of this press release.

Net cash used in operating activities for the third quarter of 2021 was $4.0 million, compared to $1.6 million for the third quarter of 2020.

At September 30, 2021, Celcuity had cash and cash equivalents of $90.4 million, compared to cash and cash equivalents of $11.6 million at December 31, 2020.

Anticipated Milestones

Celcuity expects to achieve the following potential milestones over the next twelve months:

Obtain formal feedback from the FDA on the design of its proposed Phase 3 clinical trial by early 2022.

Initiate a Phase 3 clinical trial to evaluate gedatolisib in combination with Ibrance and Faslodex in patients with ER+/HER2- advanced breast cancer in the first half of 2022, subject to the FDA feedback.

Provide an update on lifecycle development priorities for gedatolisib in the first half of 2022.

Obtain interim results from the FACT-1 and FACT-2 trials in the second half of 2022.

Webcast and Conference Call Information

The Celcuity management team will host a webcast/conference call at 4:30 p.m. ET today to discuss the third quarter financial results and provide a corporate update. To participate in the teleconference, domestic callers should dial (877) 407-0784 and international callers should dial (201) 689-8560. A live webcast presentation can also be accessed using this weblink: https://78449.themediaframe.com/dataconf/productusers/vvdb/mediaframe/46959/indexl.html. A replay of the webcast will be available on the Celcuity website following the live event.