On November 18, 2021 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that it will participate at the following investor conferences (Press release, Halozyme, NOV 18, 2021, View Source [SID1234595800]):

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33rd Annual Piper Sandler Virtual Healthcare Conference , Elaine Sun, senior vice president and chief financial officer, will represent the company in an on-demand, pre-recorded fireside chat that will be made available on the conference website starting on Monday, November 22, 2021, at 10:00 a.m. ET.
Evercore ISI 4th Annual HealthCONx Conference on Wednesday December 1, 2021, at 3:55 p.m. Eastern Time / 12:55 p.m. Pacific Time. Dr. Helen Torley, president and chief executive officer will represent the company in a virtual fireside chat.
A direct link to the presentations can be accessed through the "Investors" section of www.halozyme.com, and a recording will be made available for 6 months following the events. To access the link, please visit Halozyme’s website approximately 10 minutes prior to the presentation to register and download any necessary audio software.

On November 18, 2021 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs), reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for MT-6402 for the treatment of patients with advanced non-small cell lung cancer (NSCLC) expressing PD-L1 (Press release, Molecular Templates, NOV 18, 2021, View Source [SID1234595799]).

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"Fast Track Designation is an acknowledgement from the FDA of the potential of MT-6402 to address a significant unmet need in NSCLC," said Roger Waltzman, Molecular Templates’ Chief Medical Officer. "This designation will allow for continued contact with the FDA regarding the ongoing clinical program as well as future studies."

The Fast Track program is designed to accelerate the development and review of products such as MT-6402, which are intended to treat serious diseases and for which there is an unmet medical need. Fast Track designation enables more frequent communication with the FDA and may allow for further benefit from FDA accelerated programs such as priority review and/or rolling review.

MT-6402 is the first of MTEM’s third generation ETBs to enter the clinic. It was designed to induce potent anti-tumor effects via PD-L1 targeting through multiple mechanisms that may overcome the limitations of the PD-L1 antibodies. MT-6402 is currently being evaluated in a multi-center, open-label, dose escalation and dose expansion Phase I trial in patients with solid tumors in the United States. Patient enrollment is currently ongoing. Following determination of the maximum tolerated dose (MTD) or recommended Phase 2 dose, expansion cohorts are planned to evaluate MT-6402 as a monotherapy in tumor-specific and basket cohorts.

On November 18, 2021 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported data from two scientific posters for its Phase 2 clinical studies of VAL-083, the Company’s lead compound for the treatment of glioblastoma multiforme (GBM) (Press release, Kintara Therapeutics, NOV 18, 2021, View Source [SID1234595798]). The data are being presented at the 26th Annual Scientific Meeting of the Society for Neuro-Oncology (SNO) being held in Boston on November 18-21, 2021.

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Kintara is presenting posters on two Phase 2 clinical studies evaluating VAL-083 in patients with MGMT-unmethylated GBM as follows:

Poster CTNI-21: "Phase 2 clinical trial of dianhydrogalactitol (VAL-083) in patients with newly diagnosed MGMT-unmethylated GBM"

The first poster outlined the open-label, Phase 2 study of VAL-083 as a first-line treatment in newly-diagnosed, unmethylated GBM patients conducted at Sun Yat-sen University Cancer Center in China.

For the 25 efficacy evaluable patients enrolled with a starting dose of 30 mg/m2/day x 3 days every 21 days, progression free survival (PFS) was 8.7 months (95% confidence interval: CI 6.4-12.5) and median overall survival (mOS) was 19.1 months (CI 12.0-22.3). While not a head-to-head study, this compares favorably to historical temozolomide (TMZ) control ranging from 5.0-6.9 months PFS and 12.7-16.0 months mOS*.

The poster also highlights a case report from the study for a patient who remains progression free for more than 37 months after diagnosis. All patients have completed treatment. Adverse events have been consistent with prior studies with myelosuppression being the most common adverse event.

Poster CTNI-26: "Phase 2 study of dianhydrogalactitol (VAL-083) in patients with MGMT unmethylated, bevacizumab naïve glioblastoma in the adjuvant or recurrent setting"

The second poster outlined the two groups of patients receiving VAL-083 in the open-label, Phase 2 study in recurrent and adjuvant unmethylated GBM being conducted at the MD Anderson Cancer Center in Houston.

In the recurrent group, for the 48 efficacy evaluable patients enrolled with a starting dose of 30 mg/m2/day x 3 days every 21 days, mOS was 8.0 months (CI 6.6-10.3). While not a head-to-head study, this compares favorably to historical lomustine control mOS of 7.2 months**.

In the adjuvant group, for the 36 efficacy evaluable patients enrolled with a starting dose of 30 mg/m2/day x 3 days every 21 days, PFS was 9.5 months (CI 8.2-10.8) and mOS was 16.5 months (CI 13.6-19.3). While not a head-to-head study, this compares favorably to historical TMZ control ranging from 5.0-6.9 months PFS and 12.7-16.0 months mOS*.

All patients have completed treatment. Consistent with prior studies, myelosuppression was the most common adverse event in both recurrent GBM and in the adjuvant setting.

*Hegi et al N Eng J Med (2005); Tanguturi et al. NeuroOncol (2017); Alnahhas et al. Neurooncol Adv (2020)

** Wick et al N.Eng.J.Med (2017)

On November 18, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) reported that Gilead has exercised its options to three programs in Arcus’s clinical-stage portfolio, including both anti-TIGIT molecules, domvanalimab and AB308, as well as etrumadenant and quemliclustat (Press release, Gilead Sciences, NOV 18, 2021, View Source [SID1234595797]). The companies also added a research collaboration as described below. Today’s transaction is subject to applicable antitrust clearance under the Hart-Scott Rodino Antitrust Improvements Act and other customary closing conditions. The parties expect the transaction to close by year-end.

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Domvanalimab is an Fc-silent anti-TIGIT antibody in Phase 2 and Phase 3 studies in non-small cell lung cancer (NSCLC) and AB308 is an Fc-enabled anti-TIGIT antibody under Phase 1 evaluation. Etrumadenant is a dual adenosine A2a/A2b receptor antagonist in Phase 1 and Phase 2 studies in NSCLC, colon cancer and prostate cancer. Quemliclustat is a small molecule CD73 inhibitor in a Phase 1 study in metastatic pancreatic ductal adenocarcinoma (PDAC).

Gilead has been encouraged by early clinical data generated for each of the three programs. By opting in early to all three programs now, Gilead and Arcus are able to accelerate the clinical development and advancement of these clinical-stage molecules and facilitate the exploration of treatment combinations across the portfolios. For example, Gilead will be able to pursue potential chemotherapy-free regimens with Trodelvy (sacituzumab govitecan-hziy) in combination with therapies optioned from the Arcus portfolio. Gilead will also have the flexibility to add Gilead portfolio candidates to existing Arcus studies.

"Gilead is pursuing some of the most promising mechanisms of action in oncology today, with the aim of achieving better treatment outcomes for more patients," said Daniel O’Day, Chairman and Chief Executive Officer, Gilead Sciences. "The addition of three mid- to late-stage clinical programs into our oncology pipeline significantly expands the number of transformational medicines we can potentially deliver to people with cancer, while also enabling our pursuit of novel combinations."

"Through the expanded partnership, we will be able to leverage the combined portfolios of the two companies to enable rational exploration of unique and innovative combination therapies within a single integrated program," said Terry Rosen, Ph.D., Chief Executive Officer of Arcus. "The early exercise of Gilead’s options will now ensure that Arcus is well positioned to accelerate and expand clinical development activities so that it may deliver benefit to patients with some of the most difficult to treat cancers, including pancreatic, lung, colon and prostate."

Terms of the Exercised Options and Amendment to the Agreement

Under the terms of the parties’ Option, License and Collaboration Agreement (the "2020 Agreement"), for the three options that Gilead is exercising today, Arcus will receive option payments totaling $725 million. The parties will co-develop and share the global costs related to these programs. If the optioned molecules achieve regulatory approval, Gilead and Arcus will co-commercialize and equally share profits in the U.S. Gilead will hold exclusive rights outside the U.S., subject to any rights of Arcus’s existing collaboration partners, and Gilead will pay to Arcus tiered royalties.

With Gilead’s early option exercises for all three programs, Gilead and Arcus amended the 2020 Agreement, including as follows:

Arcus may be required to operationalize at least 50% of the clinical studies, with costs to be shared by Gilead and Arcus.
The royalties payable by Gilead to Arcus on sales for these three programs outside of the U.S. were slightly reduced. The reduced royalties range from the mid-teens to the low twenties.
Arcus will lead the discovery and early development of drug candidates against two novel research targets jointly selected by the parties.
Upon closing of the transaction for all three programs, the $100 million option continuation payment due in 2022 will not be made by Gilead.
Summary of anti-TIGIT Program

ARC-7 is a Phase 2 study evaluating patients randomly allocated to domvanalimab plus zimberelimab vs. zimberelimab alone vs. domvanalimab plus zimberelimab plus etrumadenant as first-line treatment for PD-L1 ≥ 50%, metastatic NSCLC. The study is actively enrolling with a target total enrollment of 150 patients who are being randomly allocated 1:1:1 to each group and treated until disease progression or loss of clinical benefit. Gilead and Arcus have jointly decided that results, including data on progression-free survival, will be presented at a medical conference in 2022.
ARC-10 is an ongoing registrational Phase 3 study intended to support the potential approvals of both zimberelimab monotherapy and domvanalimab plus zimberelimab in first-line, locally advanced or metastatic PD-L1≥50% NSCLC.
PACIFIC-8 is a registrational Phase 3 study with a planned initiation by the end of 2021 in collaboration with AstraZeneca. PACIFIC-8 will evaluate domvanalimab plus durvalumab, an anti-PD-L1 antibody, with curative intent in unresectable Stage 3 NSCLC, where durvalumab is standard of care.
ARC-12 is a Phase 1 study evaluating AB308 plus zimberelimab in advanced malignancies with five expansion cohorts currently open for enrollment.
Summary of ATP-Adenosine Axis (CD73 and A2a/A2b Receptor) Programs

ARC-4 is a randomized Phase 1 study evaluating etrumadenant plus zimberelimab and chemotherapy vs. zimberelimab plus chemotherapy in EGFRmut tyrosine kinase inhibitor (TKI)-relapsed and refractory NSCLC. Initial data are expected to be presented in 1H22.
ARC-6 is a Phase 1b/2 platform study in metastatic castration-resistant prostate cancer with a randomized cohort evaluating docetaxel versus docetaxel plus etrumadenant and zimberelimab. Initial results are expected in 2022.
ARC-7 is an open-label randomized Phase 2 study as noted above.
ARC-8 is an ongoing Phase 1 study evaluating quemliclustat plus zimberelimab and gemcitabine/nab-paclitaxel in first-line pancreatic cancer, with a randomized cohort comparing against quemliclustat plus gemcitabine/nab-paclitaxel. Gilead and Arcus have jointly decided that results, including data on progression-free survival, will be presented at a medical conference in 2022.
ARC-9 is a randomized Phase 1b/2, open-label, multi-center platform study to evaluate the efficacy of etrumadenant in combination with zimberelimab and FOLFOX with or without bevacizumab in second- and third-line metastatic colorectal cancer.
Additional clinical studies are expected to be initiated in 2022.
Zimberelimab, domvanalimab, AB308, etrumadenant and quemliclustat are investigational agents and have not been proven safe and efficacious. Durvalumab, docetaxel, gemcitabine/nab-paclitaxel, FOLFOX and bevacizumab are owned by companies other than Arcus and Gilead.

About the Gilead Collaboration

In May 2020, Gilead and Arcus entered into a 10-year collaboration that provided Gilead immediate rights to zimberelimab and the right to opt into all other Arcus programs arising during the collaboration term. In November 2021, Gilead and Arcus amended the collaboration in connection with Gilead’s option exercise for three of Arcus’s then-clinical stage programs. For all other programs that are in clinical development or new programs that enter clinical development thereafter, the opt-in payments are $150 million per program. Gilead’s option, on a program-by-program basis, expires after a specified period of time following the achievement of a development milestone for such program and Arcus’s delivery to Gilead of the requisite qualifying data package. Concurrent with the May 2020 collaboration agreement, Gilead and Arcus entered into a stock purchase agreement under which Gilead made a $200 million equity investment in Arcus. That stock purchase agreement was amended and restated in February 2021 in connection with Gilead’s increased equity stake in Arcus from 13% to 19.7%, with an additional $220 million investment.

Upon closing of Gilead’s exercise of its option to a program, the two companies will co-develop and share global development costs for the joint development program, subject to certain opt-out rights of Arcus in some cases and expense caps on its spending and related subsequent adjustments. For each optioned program, provided that Arcus has not exercised its opt-out rights, if any, Arcus has an option to co-promote in the United States with equal profit share. Gilead has the right to exclusively commercialize any optioned programs outside of the U.S., subject to the rights of Arcus’s existing collaboration partners to any territories, and, for clinical stage programs that Gilead has opted into, Gilead will pay Arcus tiered royalties as a percentage of revenues ranging from the mid or high teens to the low twenties.

On November 18, 2021 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), a company developing new approaches for the treatment for cancer and fibrosis, reported it has completed its review of all primary, secondary and exploratory endpoints in its successful Phase 1 clinical trial of AMP945 (Press release, Amplia Therapeutics, NOV 18, 2021, View Source;[email protected] [SID1234595796]). The results confirm that, in the trial, AMP945 was safe and well tolerated at all doses tested, exhibited excellent pharmacokinetic properties and was able to engage with its intended target, Focal Adhesion Kinase (FAK). Further details about the trial and its results are provided below.

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About the Phase 1 Trial

The clinical trial, designated as AMP945-101 and entitled "A Phase I, randomised, double blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of single and repeat doses of AMP945 administered orally to healthy adult volunteers", was conducted at Nucleus Network in Melbourne. The study was conducted under a protocol approved by the Alfred Hospital Human Research Ethics Committee (HREC) in September 2020.

The Primary Endpoints for the trial were focused on the safety and tolerability of orally administered AMP945 which were assessed by evaluating the nature, incidence and severity of adverse events, withdrawals, physical examinations, vital signs, ECGs and safety laboratory test results including assessment of biochemical and haematological markers. Secondary endpoints assessed the pharmacokinetics of AMP945. An exploratory endpoint assessed the ability of AMP945 to target FAK in skin punch biopsies.

Overall, the trial recruited 56 healthy volunteers who were dosed with either single or multiple doses of AMP945 or placebo. Single and multiple doses of AMP945 up to 125mg and 100mg respectively, were given. Multiple doses were taken once daily for seven days. To study the effect of food on absorption of AMP945, one cohort of participants was given AMP945 both before and after food. Participants in the trial ranged in age from 18-65.

Safety and Tolerability
AMP945 was well tolerated at all doses given and there were no withdrawals or serious adverse events recorded in the trial. Adverse events were generally mild or moderate and were distributed evenly across participants assigned to AMP945 or placebo. Mild headache was the most frequently observed adverse event and the majority of safety findings were considered as either not related or unlikely to be related to AMP945. Events that were considered ‘possibly’ related to AMP945 included one incidence of diarrhoea, two incidences of headache, one taste disorder and one hot flush. There were no clinically significant changes in vital signs, clinical or laboratory parameters associated with AMP945. No adverse safety signals or dose-related trends were detected in any of the parameters measured.

Pharmacokinetics
AMP945 was delivered via capsules, taken with a glass of water. Following oral dosing, the plasma half-life of AMP945 was approximately 20 hours indicating that AMP945 was both orally bioavailable and could be administered once daily. Plasma levels of AMP945 exceeded the concentrations required to inhibit the intended target (FAK) with maximum plasma levels (Cmax) being achieved after approximately 2-4 hours post dose. Exposure parameters, including Cmax and area under the curve (AUC), all increased in a dose-dependent manner. There was no evidence of any food effect on the absorption of AMP945. Studies are ongoing to measure the inhibitory activity of AMP945 on FAK in skin punch biopsies and to assess the plasma metabolite profiles of AMP945.

Pharmacodynamics
As part of the trial, skin biopsies were collected from participating healthy volunteers to evaluate the ability of AMP945 to inhibit FAK in human tissues. Analysis of these samples required Amplia to develop a sensitive assay that allowed the measurement of the active form of FAK (phospho-FAK or pFAK) in skin samples before and after AMP945 was administered. Samples collected from 24 volunteers have now been analysed and demonstrate that oral administration of AMP945 results in a decrease in active pFAK and the extent of the inhibition of FAK activity correlates with drug levels of AMP945.

In addition to demonstrating the dose-dependent reduction in pFAK in healthy volunteers, these results verify the utility of the assay used to measure pFAK in human tissue samples, confirming the availability of a test method which can be used to guide dose selection in the Company’s planned Phase 2 clinical trials of AMP945.

Amplia’s CEO and Managing Director, Dr John Lambert, commented that "Putting all the elements of this trial together, we are now able to declare it as a resounding success. Not only have we found that AMP945 has excellent pharmaceutical properties and appears to be suitable for once-daily oral dosing, we also know that it has a suitable safety profile for further development and, moreover, hits the intended target. Taking all this information together reinforces our confidence that we are on a solid foundation for Phase 2 trials of AMP945 in patients with pancreatic cancer and pulmonary fibrosis"

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics