On March 12, 2020 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of agents designed to activate immune response to cancers provided a corporate update and reported financial results for the fourth quarter and full year of 2019 (Press release, Agenus, MAR 12, 2020, View Source [SID1234555451]).

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"We are excited by the clinical responses seen in our phase 1 trial of AGEN1181 alone and in combination with our PD-1," said Garo Armen, Ph.D., Chairman and CEO, Agenus. "2020 is a year of clinical data for us; with readouts from 6 separate programs. Additionally, the data we have generated from our cervical cancer combination trial may represent the most meaningful treatment option for these patients."

AGEN1181 Clinical Responses in a Phase 1 Trial

Early data suggest that AGEN1181 could be a breakthrough in IO treatment:

Low-dose AGEN1181 (1 mg/kg) generated a complete response in advanced endometrial cancer with a poor prognosis (PD-L1[-], MSS, CD16a low affinity)
Low-dose AGEN1181 + balstilimab delivered new partial responses
Trial is in dose escalation and expansion to support rapid development
Updated data of balstilimab & zalifrelimab show 26.5% objective response rates which are durable in an all-comer, non-biomarker selected population of patients with refractory cervical cancer

Balstilimab (anti-PD-1) and zalifrelimab (anti-CTLA-4) in second line cervical cancer demonstrate 26.5% response rates (4 CRs, 5 PRs, 8 SD), responses are durable (median not yet reached 6.9mos+) and may reveal best in class treatment option
Combination receives FDA Fast Track designation for the investigation in relapsed/refractory metastatic cervical cancer
Key Milestones Expected in 2020

2 BLA filings for balstilimab (anti-PD-1) and zalifrelimab (anti-CTLA-4)
3 INDs for new discoveries targeting myeloid & macrophage biology and allogeneic iNKT cell therapy
6 clinical data readouts
Expect to trigger ~$60M in milestone payments for the year
Additional partnerships and/or collaboration discussions underway
2019: A Year of Financial and Operational Achievements

New business development transactions and milestone payments generated $183 million
$150M initially from our collaboration with Gilead ($120M in cash up front and $30M equity investment). Collected an additional $22.5M in cash milestones.
$10 million upfront from a collaboration with Urogen. Potential for ~$200M in future milestones
Completed accrual and pre-planned interim analysis of two pivotal trials to support the planned BLA filing of balstilimab and zalifrelimab in second-line cervical cancer
Launched 4 clinical programs with our first-in-class/best-in-class discoveries, including AGEN1181, AGEN1223, AGEN2373, and GS-1423 (licensed to GILD)
Advanced allogeneic cell therapy program for planned IND filing
Fourth Quarter and Full Year 2019 Financial Results

We ended 2019 with a cash balance of $62 million as compared to $53 million at December 31, 2018. Based on our year end cash balance and cash receipts in our current quarter, we expect our cash balance to be in excess of $100M at the end of the first quarter of 2020.

Cash used in operations for the quarter ended December 2019 was $32 million compared to $36 million for the same period in 2018. Cash used in operations for the year ended December 2019 was $19 million as compared to cash used in operations of $131 million for the same period in 2018.

For the fourth quarter ended December 31, 2019, we reported net loss of $31 million or $0.22 per share compared to a net loss for same period in 2018 of $49 million, or $0.40 per share. For the year ended December 31, 2019, we reported a net loss of $112 million or $0.80 per share compared to a net loss for the same period in 2018 of $162 million or $1.44 per share.

During the year ended December 2019 we recognized revenue of $150 million which includes revenue from our transaction with Gilead, non-cash royalties earned and a royalty sales milestone. This compares to revenue of $37 million for the year ended December 2018. For the year ended 2019 we also recorded $42 million of non-cash interest expense due to our transaction with HCR related to the sale of future royalties.

On March 12, 2020 Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for respiratory, cancer, and other diseases, reported financial results for its fiscal year ended December 31, 2019 and provided an update on the Company’s recent and future developments (Press release, Pieris Pharmaceuticals, MAR 12, 2020, View Source [SID1234555449]).

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"2019 was a milestone year for Pieris as we reported two positive clinical data sets, one from each of our core focus areas of respiratory diseases and immuno-oncology," said Stephen S. Yoder, President and Chief Executive Officer of Pieris. "PRS-060, an inhaled IL-4 receptor alpha antagonist for moderate-to-severe asthma that we are developing with AstraZeneca, demonstrated robust fractional exhaled nitric oxide, or FeNO, reduction in mild asthmatics in a phase 1 multiple-ascending dose study. We are very pleased with the data and are currently enrolling the final cohorts in that study to help inform the phase 2a study, which we anticipate will begin in the second half of this year. Additionally, PRS-343, a 4-1BB/HER2 bispecific for HER2-positive solid tumors, demonstrated both single-agent and checkpoint-combination anti-tumor activity, including partial responses, in heavily pre-treated patients across multiple HER2-positive tumors with correlative biomarker data indicative of 4-1BB agonism on T cells in phase 1 dose-escalation studies. These data strengthen our conviction in a 4-1BB-targeted immuno-oncology approach, and we look forward to completing the ongoing dose-escalation studies and moving this program into the next phase of development in gastric cancer. Finally, we look forward to advancing PRS-344, a 4-1BB/PD-L1 bispecific that is partnered with Servier, into the clinic."

PRS-060: In October, Pieris presented data from the phase 1b placebo-controlled multiple ascending dose study of PRS-060/AZD1402, an inhaled IL-4 receptor alpha antagonist for moderate-to-severe asthma, at the 2019 European Respiratory Society International Congress. In that analysis, PRS-060/AZD1402 was found to be safe and well tolerated at all doses, led to a statistically-significant reduction in FeNO (a marker of airway inflammation) relative to placebo, and showed dose-dependent systemic target engagement in patients with mild asthma and elevated levels of FeNO (≥ 35 ppb). Dosing of additional cohorts by Pieris is ongoing and will inform the phase 2a study; AstraZeneca and Pieris plan to initiate the phase 2a study in moderate-to-severe asthmatics in the second half of 2020. The study will be sponsored, funded, and delivered by AstraZeneca and upon completion of that study, Pieris will have the options to co-develop and, subsequently, co-commercialize PRS-060/AZD1402 in the United States.
PRS-343: In November, Pieris presented data from its phase 1 dose-escalation monotherapy study of PRS-343, a 4-1BB/HER2 bispecific for HER2-positive solid tumors, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 34th Annual Meeting. PRS-343 was safe and well tolerated at all doses and schedules tested, demonstrated anti-tumor activity in a heavily pre-treated patient population across multiple tumor types, and showed a marked increase in CD8+ T cell numbers in the tumor microenvironment of responders, indicative of 4-1BB agonism on T cells. The Company also presented emerging data from the dose-escalation phase 1 study of PRS-343 in combination with atezolizumab at the Company’s R&D day in November, showing clinical responses and correlative increases in CD8+ T cells in responding patients. Pieris plans to present detailed data from both studies at a medical meeting in the second half of this year. Based on emerging data from the ongoing clinical studies, the Company expects to initiate the next phase of PRS-343’s development in gastric cancer this year.
Preclinical Respiratory Pipeline: Beyond PRS-060, Pieris continues to advance three of four discovery programs in its five-program respiratory collaboration with AstraZeneca. AstraZeneca will have the option to initiate the fourth discovery program in the collaboration this year. The Company also continues to advance several proprietary discovery-stage respiratory programs. Pieris expects to share data and rationale for advancement of one of its proprietary programs at a medical meeting in the second half of this year.
Asthma Research Collaboration with the University of Pittsburgh: As part of the Company’s commitment to building a novel respiratory pipeline, in the fourth quarter, Pieris entered into research collaboration with the laboratories of University of Pittsburgh Professors Sally Wenzel, MD, and Anuradha Ray, PhD, focused on comprehensive immune phenotyping of severe asthmatic patients. Key objectives of the multi-year collaboration include patient stratification strategies for more streamlined development of therapeutic interventions as well as identifying and validating novel asthma targets.
Immuno-oncology Pipeline: Pieris plans to file an IND application for PRS-344, a 4-1BB/PD-L1 bispecific that the Company is developing as part of its collaboration with Servier, in the first half of this year. Pieris holds exclusive commercialization rights for PRS-344 in the United States and will receive royalties on ex-U.S. sales for this program. The Company’s immuno-oncology collaboration with Seattle Genetics continues to progress on schedule.
Private Placement: In the fourth quarter, the Company completed a $32 million private placement with new and existing healthcare-focused institutional investors that resulted in a year-end cash and investment position exceeding $100 million.
Fiscal Year Financial Update:

Cash Position – Cash, cash equivalents, and investments totaled $104.2 million for the year ended December 31, 2019, compared to a cash, cash equivalents, and investments balance of $128.1 million for the year ended December 31, 2018. The decrease in cash, cash equivalents, and investments was primarily due to the Company’s operational needs during 2019, offset by proceeds from the private placement financing completed in November 2019.

R&D Expense – R&D expenses were $55.0 million for the year ended December 31, 2019, compared to $41.5 million for the year ended December 31, 2018. The increase in R&D expenses was primarily due to higher manufacturing costs supporting planned and ongoing clinical studies as well as higher personnel, facility, and IT costs supporting the ongoing advancement of the Company’s pipeline. The increase was offset by a decline in royalty expenses due to lower upfront and milestone payments compared to 2018.

G&A Expense – G&A expenses remained flat at $18.4 million for both years ended December 31, 2019 and December 31, 2018. The Company incurred higher hardware and software costs to support operations growth and efficiency, and higher audit and tax fees due to new accounting regulations and internal control requirements. These costs were offset by both lower professional service fees as the Company better leveraged internal resources in 2019 and lower facilities and IT costs attributed to G&A functions.

Interest Income – Interest income was $1.7 million for the year ended December 31, 2019, compared to $2.0 million earned for the year ended December 31, 2018. The decrease was due to lower average cash amounts invested during the year and declining interest rates on investments in 2019.

Net Loss Attributable to Common Stockholders – Net loss attributable to common stockholders was $28.3 million or $(0.56) per share for the year ended December 31, 2019, compared to a net loss of $26.8 million or $(0.50) per share for the year ended December 31, 2018.

Conference Call:

Pieris management will host a conference call beginning at 8:00 AM Eastern Daylight Time on Thursday, March 12, 2020, to discuss the full year financial results and provide a corporate update. Individuals can join the call by dialing +1-877-407-8920 (US & Canada) or +1-412-902-1010 (International). An archived replay of the call will be available by dialing +1-877-660-6853 (US & Canada) or +1-201-612-7415 (International) and providing the Conference ID #: 13661472.

On March 12, 2020 Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to invent breakthrough protein degrader medicines for patients, reported the closing of a $102 million Series C financing (Press release, Kymera Therapeutics, MAR 12, 2020, View Source [SID1234555448]). The round was led by Biotechnology Value Fund (BVF) and Redmile Group with participation from Wellington Management Company, Bain Capital Life Sciences, funds managed by Janus Henderson Investors and BlackRock, Rock Springs Capital and a large US-based, healthcare-focused fund. Existing investors also participated in the round.

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Kymera also received a strategic investment from The Leukemia & Lymphoma Society‘s Therapy Acceleration Program (LLS TAP) directed toward advancing the company’s work to treat blood-based cancers.

"We are very excited to be joined by a top-tier group of investors as we continue on our path to become a fully integrated biotech company," said Nello Mainolfi, PhD, co-founder, President and CEO of Kymera Therapeutics. "We are well capitalized to advance up to three programs to the clinic by next year, while we continue to enhance our best-in-class platform to unlock new biology and invent new medicines."

Kymera’s Pegasus targeted protein degradation platform harnesses the body’s natural protein recycling machinery to degrade disease-causing proteins, with a focus on un-drugged nodes in validated pathways currently inaccessible with conventional therapeutics.

Kymera‘s lead program targets IRAK4, a protein known to play a significant role in inflammation mediated by toll-like and IL-1 receptors. Kymera is planning to advance its IRAK4 degrader program in a variety of autoinflammatory and autoimmune diseases, as well as in precision-medicine targeted oncology indications. The company is also developing novel protein degrader therapies to target STAT3, an un-drugged oncogenic transcription factor as well as a driver of inflammation and fibrosis, in a range of cancers and chronic diseases.

"Targeted protein degradation is one of the most promising new therapeutic modalities, with the potential to transform medicine as we know it. Kymera is leading the way with an incredible team, a sophisticated drug discovery platform and important new protein degrader therapies designed to address the most elusive drug targets" said Bruce Booth, DPhil, co-founder, Chairman of the Board of Kymera Therapeutics and partner at Atlas Venture.

On March 12, 2020 AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada) reported high-level results from the Phase III GY004 trial, led by NRG Oncology and sponsored by the US National Cancer Institute (NCI), that examined primarily the efficacy and safety of the potential new medicine cediranib added to Lynparza (olaparib) versus platinum-based chemotherapy in patients with platinum-sensitive relapsed ovarian cancer (Press release, AstraZeneca, MAR 12, 2020, View Source [SID1234555443]). Ovarian cancer is the eighth most common cause of death from cancer in women worldwide.

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The trial did not meet the primary endpoint in the intent-to-treat (ITT) population of a statistically significant improvement in progression-free survival (PFS) with cediranib added to Lynparza versus platinum-based chemotherapy. Cediranib is an oral vascular endothelial growth factor receptor (VEGFR) inhibitor, which blocks the growth of blood vessels supporting tumour growth.

José Baselga, Executive Vice President, Oncology R&D, said: "Despite these disappointing results, we remain committed to expanding on the benefits already demonstrated with Lynparza for patients with advanced ovarian cancer. We will work closely with NRG Oncology and the NCI to review the full results to inform our ongoing research."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "Ovarian cancer is one of the most difficult tumours to diagnose and treat early. AstraZeneca, MSD and our partners will continue to explore ways to help patients through our joint clinical trial development programme."

The safety and tolerability profiles observed in GY004 were generally consistent with those known for each medicine.

The NCI and NRG Oncology will present the full data at a forthcoming medical meeting.

Ovarian cancer

Ovarian cancer is the eighth most common cause of death from cancer in women worldwide.1 In 2018, there were nearly 300,000 new cases diagnosed2 and around 185,000 deaths.1 Most women are diagnosed with advanced (Stage III or IV) ovarian cancer and have a five-year survival rate of approximately 30%.3 The primary aim of treatment in relapsed ovarian cancer is to delay progression of the disease for as long as possible, therefore increasing the time to re-initiation of chemotherapy with its associated toxicities, and maintaining quality of life for these patients.4,5,6

GY004

GY004 is an open-label, randomised, multicentre, Phase III trial testing the efficacy and safety of the potential new medicine cediranib added to Lynparza, versus Lynparza monotherapy versus standard platinum-based chemotherapy in patients with recurrent platinum-sensitive ovarian cancer, fallopian tube, or primary peritoneal cancer patients, with or without a BRCA mutation.

The GY004 trial is led by NRG Oncology, a non-profit research organisation funded by the NCI, in collaboration with AstraZeneca. The NCI is part of the National Institutes of Health. AstraZeneca provided both cediranib and Lynparza to support the trial through a Cooperative Research and Development Agreement with the NCI.

Lynparza

Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair, such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in 73 countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in 58 countries, including the US and Japan, for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer. In 2019, Lynparza was additionally approved in the US for the treatment of germline BRCA-mutated metastatic pancreatic cancer. Regulatory reviews are underway in other jurisdictions for ovarian, breast, pancreatic and prostate cancers.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for the treatment of advanced ovarian cancer, metastatic breast cancer and pancreatic cancer. It has been used to treat over 30,000 patients worldwide. Lynparza has the broadest and most advanced clinical-trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

Cediranib

Cediranib is an oral vascular endothelial growth factor (VEGF) receptor inhibitor that has demonstrated efficacy as a monotherapy and in combination in various cancers. Cediranib has shown anti-tumour activity in many cancers, including ovarian, breast, colorectal, renal, lung, sarcoma and glioblastoma. Cediranib is being evaluated in combination with Lynparza in advanced ovarian cancer in the Phase II CONCERTO trial, Phase II/III GY005 trial (sponsored by the NCI) and Phase III ICON9 trial (sponsored by University College, London).

The AstraZeneca and MSD strategic oncology collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With six new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investment that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

On March 11, 2020, IDEAYA Biosciences, Inc. (the "Company") entered into a Clinical Trial Collaboration and Supply Agreement (the "Agreement") with Pfizer Inc. ("Pfizer"), pursuant to which the Company and Pfizer will collaborate on a portion of the Company’s Phase 1/2 study in Metastatic Uveal Melanoma (MUM) and other solid tumors harboring activating GNAQ or GNA11 hotspot mutations, in each case pertaining to the clinical evaluation of the Company’s IDE196 compound in combination with Pfizer’s MEK inhibitor, binimetinib (the "Combination Study") (Filing, 8-K, Ideaya Biosciences, MAR 11, 2020, View Source [SID1234555643]). Pursuant to the Agreement, the Company is the sponsor of the Combination Study and the Company will provide the Company’s IDE196 compound and will pay for the costs of the Combination Study. Pfizer will provide binimetinib for the Combination Study at no cost to the Company. The Company and Pfizer will jointly own clinical data from the Combination Study and all inventions relating to the combined use of IDE196 and binimetinib. The Company and Pfizer will form a joint development committee responsible for coordinating all regulatory and other activities under the Agreement.

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