On October 9, 2020 Exelixis, Inc. (NASDAQ: EXEL) reported new data that support the ongoing clinical development of XL092, the company’s next-generation oral tyrosine kinase inhibitor that targets VEGF receptors, MET, AXL, MER, and other kinases implicated in cancer’s growth and spread (Press release, Exelixis, OCT 9, 2020, View Source [SID1234568268]). The new data will be presented in a poster discussion session (Abstract 33) as part of the 32nd EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium, which is being held virtually October 24-25; abstracts for the meeting were released earlier today.

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"When the XL092 program began, we wanted to develop a novel tyrosine kinase inhibitor that retained the target profile of cabozantinib, our flagship medicine that is now a global oncology franchise, while also improving on certain important characteristics"

"When the XL092 program began, we wanted to develop a novel tyrosine kinase inhibitor that retained the target profile of cabozantinib, our flagship medicine that is now a global oncology franchise, while also improving on certain important characteristics," said Peter Lamb, Ph.D., Executive Vice President of Scientific Strategy and Chief Scientific Officer of Exelixis. "The data to be presented at the ENA Symposium suggest XL092 has a desirable therapeutic profile that pairs the potential for significant anti-tumor activity with a much shorter clinical half-life than cabozantinib. The data also support a potential synergistic effect for XL092 in combination with immune checkpoint inhibitors, which is why we’re excited to expand our ongoing phase 1 clinical trial to include an exploration of the combination of XL092 and atezolizumab in multiple solid tumors."

The abstract released today provides a summary of results from a detailed characterization of XL092 in cancer cell lines and animal tumor models, as well as initial PK data from the ongoing phase 1 trial of the compound. Additional data will be presented in the poster discussion, which is scheduled to begin at 22:40 CEST / 4:40 p.m. EDT / 1:40 p.m. PDT on Saturday, October 24. Key findings included in the abstract are:

XL092 is an ATP-competitive inhibitor of multiple receptor tyrosine kinases including MET, VEGFR2, AXL and MER, with IC50 values in cell-based assays of 15, 1.6, 3.4, and 7.2 nM, respectively.
In xenograft studies, XL092 caused substantial tumor growth inhibition following 10 mg/kg daily oral dosing for 14 days, which was accompanied by significant inhibition of MET, AXL and VEGFR2 phosphorylation.
When XL092 was combined with an immune checkpoint inhibitor (ICI) in a syngeneic tumor model, the combination was significantly more efficacious than either XL092 or anti-PD1 alone.
PK data from the ongoing phase 1 clinical trial assessing daily dosing of XL092 in patients with advanced solid tumors shows a terminal half-life of 24 hours versus a 99-hour terminal half-life for cabozantinib.
The ongoing phase 1 trial (NCT03845166) is a multi-center study designed to evaluate the pharmacokinetics, safety, tolerability, and preliminary anti-tumor activity of XL092, both as a single agent and in combination with ICIs. The study protocol was recently amended to include dose-escalation and expansion cohorts for XL092 in combination with the ICI atezolizumab (TECENTRIQ). The dose-escalation evaluation of XL092 as a single agent is ongoing, and Exelixis anticipates patient enrollment in the dose-escalation evaluation of the combination regimen imminently. As recommended doses of single-agent XL092 and XL092 in combination with atezolizumab are established, the trial will proceed to enroll expansion cohorts in patients with clear cell and non-clear cell renal cell carcinoma, hormone-receptor positive breast cancer, and metastatic castration-resistant prostate cancer.

About XL092

XL092 is a next-generation oral tyrosine kinase inhibitor that targets VEGF receptors, MET, AXL, MER, and other kinases implicated in cancer’s growth and spread. In designing XL092, Exelixis sought to build upon the experience and target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including clinical half-life. The compound is the subject of an ongoing phase 1 trial (NCT03845166) evaluating its pharmacokinetics, safety, tolerability, and preliminary anti-tumor activity when administered alone and in combination with the ICI atezolizumab (TECENTRIQ); pending positive data, further development is planned.

On October 9, 2020 ADC Therapeutics SA (NYSE: ADCT), a late clinical-stage oncology-focused biotechnology company pioneering the development and commercialization of highly potent and targeted antibody drug conjugates for patients with hematological malignancies and solid tumors, reported the underwriters in its recent upsized public offering of 6,000,000 common shares, which closed on September 28, 2020, have exercised in full their option to purchase an additional 900,000 common shares from the selling shareholders at the public offering price of $34.00 per share, less underwriting discounts and commissions (Press release, ADC Therapeutics, OCT 9, 2020, View Source [SID1234568265]). ADC Therapeutics did not receive any proceeds from the sale of shares by the selling shareholders.

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Morgan Stanley, BofA Securities and Cowen acted as joint book-running managers for the offering. RBC Capital Markets acted as co-manager for the offering.

The offering is being made only by means of a prospectus. Copies of the prospectus relating to the offering may be obtained from Morgan Stanley & Co. LLC, Attn: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014 or by email at [email protected]; BofA Securities, Inc., NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, NC 28255-0001, Attn: Prospectus Department, or by email at [email protected]; or Cowen and Company, LLC, c/o Broadridge Financial Solutions, Attn: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (833) 297-2926 or by email at [email protected].

A registration statement relating to these securities has been filed with, and declared effective by, the U.S. Securities and Exchange Commission. 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 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. There is no intention or permission to publicly offer, solicit, sell or advertise, directly or indirectly, any securities of ADC Therapeutics SA, such as the common shares, in or into Switzerland within the meaning of the Swiss Financial Services Act ("FinSA") and these securities will not be listed or admitted to trading on the SIX Swiss Exchange or on any other regulated trading venue (exchange or multilateral trading facility) in Switzerland. Neither this document nor any other offering or marketing material relating to these securities, such as the common shares, constitutes or will constitute a prospectus pursuant to the FinSA, and neither this document nor any other offering or marketing material relating to the common shares constitutes a prospectus pursuant to the FinSA, and neither this document nor any other offering or marketing material relating to the common shares may be publicly distributed or otherwise made publicly available in Switzerland.

On October 9, 2020 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported that it will present initial data from the ongoing dose escalation portion of its Phase 1 clinical trial of SY-5609, its highly selective and potent oral cyclin-dependent kinase 7 (CDK7) inhibitor, in patients with select solid tumors (Press release, Syros Pharmaceuticals, OCT 9, 2020, View Source [SID1234568261]). The data will be presented in a poster session at the 32nd EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium, taking place virtually October 24-25, 2020, and will include data on safety, pharmacokinetics and pharmacodynamics.

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The abstract is now available on the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) conference website at View Source The presentation will be available for on-demand viewing on the ENA website starting Saturday, Oct. 24, 2020.

Details of the poster presentation are as follows:

Presentation Title: Early evidence of dose-dependent pharmacodynamic activity following treatment with SY-5609, a highly selective and potent oral CDK7 inhibitor, in patients with advanced solid tumors
Session Title: New Drugs
Presenter: Kyriakos P. Papadopoulos, M.D., South Texas Accelerated Research Therapeutics
Abstract Number: 180

On October 9, 2020 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported that leading science and technology company and existing shareholder Merck KGaA, Darmstadt, Germany, through its wholly owned subsidiary, Ares Trading S.A., has elected to voluntarily convert a convertible note with an outstanding principal balance of $25 million to increase its stake in Precigen from approximately 11.6% to 14.8% of outstanding shares, remaining as Precigen’s second largest shareholder (Press release, Precigen, OCT 9, 2020, View Source [SID1234568260]). As previously announced in December 2018, Merck KGaA, Darmstadt, Germany, reassigned to Precigen exclusive chimeric antigen receptor T-cell (CAR-T) development rights that were part of an earlier transaction between the companies. This reassignment allowed Precigen to regain full autonomous development of its proprietary CAR-T technology platform in exchange for $150 million in stock and a $25 million convertible note, allowing Merck KGaA, Darmstadt, Germany, to maintain an investment in the future potential of Precigen’s next-generation CAR-T development. The convertible note, which would have otherwise converted in December of 2020, is being exercised ahead of its designated maturity.

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"In line with Merck KGaA, Darmstadt, Germany’s mission to discover innovative therapies with transformative results, we are pleased to continue our relationship with Dr. Sabzevari and her team as they advance Precigen’s pipeline of next generation CAR-T therapies," said Belén Garijo, Vice Chair of the Executive Board and Deputy CEO of Merck KGaA, Darmstadt, Germany, and CEO of Healthcare. "We look forward to continuing a productive relationship with Precigen leading to better health outcomes for patients with a broad range of cancers."

The relationship between Precigen and Merck KGaA, Darmstadt, Germany is longstanding, dating back to 2015 when the two companies signed an agreement to develop and commercialize CAR-T cancer therapies utilizing Precigen’s proprietary Sleeping Beauty non-viral gene integration technology. This technology has evolved into Precigen’s UltraCAR-T next generation CAR-T therapies, which have demonstrated superior efficacy in preclinical studies and combine rapid manufacturing to improve time to treatment. Two UltraCAR-T therapies are currently being evaluated in Phase 1 clinical trials, including PRGN-3005 in ovarian cancer and PRGN-3006 in acute myeloid leukemia (AML).

"We welcome a strengthened relationship with Merck KGaA, Darmstadt, Germany, a recognized leader in oncology and patient care, as it increases its ownership position in Precigen," said Helen Sabzevari, PhD, President and CEO of Precigen. "We look forward to building value for all of our stakeholders through the clinical milestones we have planned over the next year and beyond."

On October 9, 2020 Exelixis, Inc. (Nasdaq: EXEL) and Aurigene Discovery Technologies Limited (Aurigene) reported disclosed new preclinical data showing that AUR102 has potent anti-tumor activity in a large panel of cancer cell lines (Press release, Aurigene Discovery, OCT 9, 2020, View Source [SID1234568259]). AUR102 is a potent, selective, and orally bioavailable covalent inhibitor of cyclin-dependent kinase 7 (CDK7), which is an important regulator of the cellular transcriptional and cell cycle machinery . Exelixis has an exclusive option for AUR102 under its July 2019 exclusive collaboration, option and license agreement with Aurigene. The new data will be presented in a poster (Abstract 170) at the 32nd EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium, which is being held virtually on October 24-25, 2020.

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"CDK7 plays a critical role in regulating cellular transcription and cell cycle machinery, making it an exciting target for cancer therapy"

"CDK7 plays a critical role in regulating cellular transcription and cell cycle machinery, making it an exciting target for cancer therapy," said Murali Ramachandra, Ph.D., Chief Executive Officer of Aurigene. "The data to be presented at ENA 2020 demonstrate that AUR102 effectively engages CDK7 and inhibits a key mediator of the cell cycle and transcription. The ability to inhibit CDK7 activity with an orally available therapeutic such as AUR102 holds great potential to improve care and outcomes for patients with diverse cancer indications, including breast cancer, prostate cancer, leukemia and lymphoma."

The abstract provides a summary of results from a detailed characterization of AUR102 in cancer cell lines and animal tumor models. Additional data will be presented in the poster. Key findings included in the abstract are:
• AUR102 exhibited potent anti-proliferative activity in a large panel of cell lines with induction of cell death in cell lines derived from multiple cancer types.
• The observed anti-proliferative activity correlated with cellular CDK7 target engagement and decreased levels of P-Ser5 RNAPII, a key mediator of transcription.
• AUR102 studies showed synergy when used in combination with multiple chemotherapies.
• Oral dosing with AUR102 resulted in dose-dependent anti-tumor activity, including complete tumor regression in diffuse large B-cell lymphoma, acute myeloid leukemia, and triple-negative breast cancer xenograft models.
• Inhibition of tumor growth was accompanied by complete target engagement as demonstrated in a parallel PK-PD study.
• AUR102 significantly impacts several pathways and key cancer driver and immune-response genes.

The study authors conclude that the data support clinical evaluation of AUR102 as a single agent and in combination with chemotherapies for the treatment of cancer.

"The exciting AUR102 data to be presented at ENA 2020 provide further validation of our partnering strategy, which gives us multiple opportunities to build a pipeline of best-in-class cancer therapies," said Peter Lamb, Ph.D., Executive Vice President of Scientific Strategy and Chief Scientific Officer of Exelixis. "AUR102 could be the subject of an Investigational New Drug filing later this year, which would be an important value driver for the program itself and for our collaboration with Aurigene. We commend the Aurigene team on their ongoing success in building a robust body of data supporting the broad clinical potential of AUR102."

Under the terms of the July 2019 agreement, Exelixis made an upfront payment of $10 million for exclusive options to license three preexisting programs from Aurigene. In addition, Exelixis and Aurigene initiated three Aurigene-led drug discovery programs on mutually agreed upon targets, in exchange for additional upfront option payments of $2.5 million per program. Exelixis is also contributing research funding to Aurigene to facilitate discovery and preclinical development work on all six programs. As the programs mature, Exelixis will have the opportunity to exercise an exclusive option for each program up until the time of Investigational New Drug (IND) filing acceptance. If Exelixis decides to exercise an option, it will make an option exercise payment to Aurigene and assume responsibility for that program’s future clinical development and commercialization including global manufacturing. Aurigene will be eligible for clinical development, regulatory, and sales milestones, as well as royalties on sales. Under the terms of the agreement, Aurigene retains limited development and commercial rights for India and Russia.