On December 19, 2019 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology (I-O) company with a pipeline of immune checkpoint antibodies, adoptive cell therapies1 and cancer vaccines, reported the first patient dosed with AGEN1181, an anti-CTLA-4 antibody, in combination with balstilimab, Agenus’ PD-1 inhibitor (Press release, Agenus, DEC 19, 2019, View Source [SID1234552496]). Agenus began this study as a monotherapy in patients with advanced solid tumors within a Phase 1 dose escalation study (NCT03860272) in April 2019.

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The first patients to be treated with AGEN1181 as a monotherapy as well as the combination trial with PD-1 were dosed by Dr. Steven O’Day, Executive Director of the John Wayne Cancer Institute & Cancer Clinic, and a pioneer in delivering immune therapies to patients with cancer.

"AGEN1181, with its potential for enhanced immune activation and tumor fighting abilities, may bring superior benefit to a broader group of patients compared to first generation anti-CTLA-4 antibodies," said Dr. O’Day. "The pre-clinical data suggest the superiority of this molecule as a monotherapy and in combination with anti-PD-1, like balstilimab. Furthermore, AGEN1181 was designed to bring benefit to a broad population of patients both who respond to first generation molecules and those who do not respond due to a genetic polymorphism. Expanding the important immune priming benefit of CTLA-4 to a broad group of patients would be outstanding. I am thrilled to be working with this compound."

Balstilimab, the company’s proprietary anti-PD-1 antibody, is currently being evaluated as a monotherapy and in combination with zalfrelimab (a first generation CTLA-4) in trials designed to support a planned BLA filing in 2020 for patients with relapsed/refractory cervical cancer.

This expanded trial is another example of Agenus’ ability to rapidly advance its novel pipeline. Next-Gen CTLA-4 is a novel antibody from Agenus’ discovery engine, and with its own PD-1 molecule, Agenus has been able to move this important combination into the clinic with a high sense of urgency.

About AGEN1181
AGEN1181, a novel ‘Fc engineered’ antibody with potential for enhanced anti-tumor functions, is specifically designed to boost cancer killing immune cells and deplete intratumoral regulatory T cells that promote immune evasion. By enhancing binding to a specific Fc receptor, FcγRIIIA, on antigen-presenting cells or natural killer cells, AGEN1181 significantly enhances the therapeutic potential of anti-CTLA-4 therapy leveraging novel mechanisms that are not captured by the first-generation anti-CTLA-4 therapies. AGEN1181’s Fc engineered backbone improves the cross-talk between antigen-presenting cells and T cells, to enable optimal T cell priming, activation and formation of durable memory responses. Moreover, AGEN1181 enhanced binding to FcγRIIIA, significantly increases the potential to deplete intratumoral regulatory T cells, a significant barrier to successful anti-cancer immune responses. Notably, AGEN1181 is engineered to strongly bind both the low affinity and high affinity FcγRIIIA polymorphisms, unlike first generation molecules which weakly bind the low affinity polymorphism. AGEN1181 is designed to expand the benefit to an additional ~40% of patients with the low affinity polymorphism and enhance the benefits of CTLA-4 in all patients.

On December 19, 2019 Exelixis, Inc. (NASDAQ:EXEL) reported a collaboration agreement with Roche to evaluate cabozantinib (CABOMETYX), Exelixis’ small molecule inhibitor of receptor tyrosine kinases, in combination with atezolizumab (TECENTRIQ), Roche’s PD-L1 immune checkpoint inhibitor, in patients with locally advanced or metastatic solid tumors (Press release, Exelixis, DEC 19, 2019, View Source [SID1234552513]). The clinical program, which will be co-funded by the companies, is expected to include three phase 3 pivotal trials in advanced non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC) and renal cell carcinoma (RCC).

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"Encouraging phase 1 data suggests this combination of cabozantinib and atezolizumab may improve outcomes for patients with prostate, lung and kidney cancers, and we look forward to collaborating with Roche to learn more in these pivotal trials," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "This clinical collaboration is an important further step in our committed efforts to maximize the value of the cabozantinib franchise through these cost-sharing clinical collaborations in additional high-impact indications, while building value with new compounds from internal and external sources in 2020 and beyond."

The clinical development collaboration builds on encouraging activity observed in the phase 1b COSMIC-021 trial. The trial is currently enrolling 24 expansion cohorts in 12 tumor types including RCC, NSCLC and CRPC.

TECENTRIQ (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide.

About Exelixis’ Collaboration with Ipsen

On February 29, 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan. On December 21, 2016, this agreement was amended to include commercialization rights for Ipsen in Canada. Under the parties’ collaboration agreement, if Ipsen opts to participate in funding these phase 3 trials, or future studies, Ipsen will have access to the respective study results to support potential future regulatory submissions in their territory.

About Exelixis’ Collaboration with Takeda

On January 30, 2017, Exelixis and Takeda jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications in Japan. Under the parties’ collaboration agreement, if Takeda opts to participate in funding these phase 3 trials, or future studies, Takeda will have access to the respective study results to support potential future regulatory submissions in their territory.

Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

U.S. Important Safety Information

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.
Perforations and Fistulas: GastrointestinaI (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.
Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.
Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.
Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.
Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.
Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 28 days prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution.
Wound Complications: Wound complications were reported with CABOMETYX. Stop CABOMETYX at least 28 days prior to scheduled surgery. Resume CABOMETYX after surgery based on clinical judgment of adequate wound healing. Withhold CABOMETYX in patients with dehiscence or wound healing complications requiring medical intervention.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.
Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.
Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.
Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.
Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

On December 19, 2019 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX, TSX-V: EPI), a pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported financial results for the fiscal year ended September 30, 2019 (Press release, ESSA, DEC 19, 2019, View Source [SID1234552533]). All references to "$" in this release refer to United States dollars, unless otherwise indicated.

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"This past year was ESSA’s most significant year of progress towards its goal of developing a novel prostate cancer therapy. Our discovery efforts led to the selection of a next generation N-terminal domain inhibitor of the androgen receptor ("aniten"), EPI-7386, that was nominated as the IND candidate. Preclinically, this potent compound exhibits a long half-life, and excellent pharmaceutical properties, while also demonstrating on-target specificity and anti-tumor activity against prostate cancer cell lines and animal models resistant to currently used anti-androgens. Preparations for an IND filing continue to advance and we remain on track to file the IND in the first quarter of 2020 with an initiation of the Phase 1 study of EPI-7386 expected in the first half of 2020," stated David Parkinson, MD, President and CEO of ESSA.

Dr. Parkinson continued, "With the $56 million raised through the acquisition of Realm Therapeutics, plc and the subsequent private placement, the Company has sufficient funds to complete the Phase 1 monotherapy dose-escalation study and an expansion phase to that study. In addition, the Company believes it is funded to be able to conduct a combination study of EPI-7386 with currently utilized antiandrogens in prostate cancer patients with earlier stages of the disease. 2020 will be another important year as we commence clinical development of EPI-7386 as a single agent in advanced prostate cancer as well as in combination with standard of care anti-androgens in earlier lines of therapy. The Phase I clinical trial will be conducted in men whose tumors are progressing (and therefore PSA levels are rising) despite therapy with one of the latest generation anti-androgen therapies. While patients will be selected for the trial on the basis of clinical considerations, a series of biological studies will characterize their individual tumor biology. In addition, we will continue the characterization of other aniten molecules in our pre-clinical pipeline."

Clinical and Corporate Highlights for 2019 Fiscal Year

On March 28, 2019, the Company nominated EPI-7386 as the lead clinical candidate for the treatment of metastatic castration-resistant prostate cancer ("mCRPC")
On July 15, 2019, the Company appointed Dr. Alessandra Cesano as Chief Medical Officer
On July 31, 2019, the Company completed the acquisition of Realm Therapeutics, plc ("Realm"), which provided the Company with approximately $20M in additional funds
On August 23, 2019, the Company closed an equity financing for gross proceeds of $36 million
In October, the Company paid off the balance of its $3.6M debt facility, leaving the Company with no outstanding debt
Throughout the year, at multiple scientific conferences, the Company presented preclinical data characterizing the preclinical profile of EPI-7386 in various prostate cancer preclinical models
Summary Financial Results

Net Income (Loss). ESSA recorded a net loss of $10.4 million ($1.24 loss per common share based on 8,433,441 weighted average common shares outstanding) for the year ended September 30, 2019, compared to a net loss of $11.6 million ($2.55 loss per common share based on 4,566,519 weighted average common shares outstanding) for the year ended September 30, 2018. The net loss for the fourth quarter ended September 30, 2019 was $1.0 million compared to a net loss of $2.3 million for the fourth quarter ended September 30, 2018.

Research and Development ("R&D") expenditures. R&D expenditures for the year ended September 30, 2019 were $6.7 million compared to $4.9 million for the year ended September 30, 2018. For the fourth quarter ended September 30, 2019, R&D expenditures were $2.0 million (net and gross), as compared to $0.9 million net of grants ($1.2 million gross) for the fourth quarter ended September 30, 2018. The increase in R&D expenditures for the full year and fourth quarter were primarily related to ESSA’s efforts in preparing an Investigational New Drug ("IND") application for its recently nominated clinical candidate, EPI-7386. Costs in the comparative period included preclinical research related to the Company’s next-generation aniten compounds.

General and administration ("G&A") expenditures. G&A expenditures for the year ended September 30, 2019 were $5.5 million compared to $5.9 million for the year ended September 30, 2018. For the fourth quarter ended September 30, 2018, G&A expenditures were $1.3 million, compared to $1.2 million for the fourth quarter ended September 30, 2018. The decrease in the full year is the result of a reduction in share-based payments, rent expense, and professional fees. The increase in the fourth quarter is a result of increased corporate activity following the acquisition of Realm, including directors fees, investor relations, and regulatory fees.
Liquidity and Outstanding Share Capital
Cash on hand at September 30, 2019 was $53.3 million, with working capital of $48.7 million, reflecting the aggregate gross proceeds of the completed August 2019 financing of $36 million, the acquisition of Realm which provided the Company with $22.2 million in cash, less operating expenses in the intervening period.

As of September 30, 2019, the Company had 20,762,374 common shares issued and outstanding.

In addition, as of September 30, 2019 there were 12,393,092 common shares issuable upon the exercise of warrants and broker warrants. This includes 11,919,404 prefunded warrants at an exercise price of $0.0001, and 473,688 other warrants at a weighted average exercise price of $34.36. There are 5,314,000 common shares issuable upon the exercise of outstanding stock options at a weighted-average exercise price of $3.19 per common share.

On December 19, 2019 BridgeBio Pharma, Inc. (Nasdaq: BBIO) reported that it will present at the 38th Annual J.P. Morgan Healthcare Conference on Monday, January 13, 2020 at 3 PM (PST) in San Francisco (Press release, BridgeBio, DEC 19, 2019, View Source [SID1234576261]).

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The presentation will be webcast live and can be accessed at www.bridgebio.com on the For Investors page under News & Events. The webcast will be available for replay for 30 days.

On December 19, 2019 Agilent Technologies Inc. (NYSE: A) reported the following presentation will be webcast for the investor community (Press release, Agilent, DEC 19, 2019, https://www.agilent.com/about/newsroom/presrel/2019/19dec-gp19028.html [SID1234552497]):

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What: 38th Annual J.P. Morgan Healthcare Conference
Where: The Westin St. Francis Hotel, San Francisco, California
When: Tuesday, Jan. 14, 2020 at 2:30 p.m. PT
Who: Mike McMullen, Agilent President and CEO