On November 3, 2021 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported updated clinical data from a Phase 1 study of tidutamab, an SSTR2 x CD3 bispecific antibody, in patients with neuroendocrine tumors (NETs) (Press release, Xencor, NOV 3, 2021, View Source [SID1234594273]). The data will be presented during the North American Neuroendocrine Tumor Society’s 2021 Multidisciplinary NET Medical Virtual Symposium (NANETS).

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"The Phase 1 study of tidutamab in patients with neuroendocrine tumors informed our view that an XmAb CD3 bispecific antibody is generally well tolerated in solid tumors, with a low incidence and severity of CRS, and can induce meaningful biological activity in a challenging disease setting," said Allen Yang, M.D., Ph.D., senior vice president and chief medical officer at Xencor. "Importantly, we identified a recommended dose for continued study, and a Phase 1b/2 study has been opened to evaluate tidutamab as a potential treatment option for patients with Merkel cell carcinoma and small cell lung cancer, SSTR2-expressing tumor types known to be responsive to immunotherapy."

A poster with data from the study is available in the NANETS Virtual Poster Hall, and it will be made available under Archived Scientific Presentations on the Events & Presentations page in the Investors section of www.xencor.com. In addition to the poster, these results will be presented during the Clinical Abstracts session, which begins at 1:25 p.m. ET on Saturday, November 6, 2021.

Key Highlights

The primary objectives of the Phase 1 study were to determine the safety and tolerability profile of tidutamab in patients with advanced, well-differentiated NETs of pancreatic, gastrointestinal, lung and undetermined origin, and to identify the maximum tolerated dose and/or recommended dosing regimen for continued study, which was determined to be a 0.3 mcg/kg priming dose followed by 1.0 mcg/kg on subsequent dosing days.

At data cut-off in August 2021, 41 patients with neuroendocrine tumors, with the initial lesion location in the pancreas (46%), intestine (22%), lung (20%), and other GEP-NET or unknown (12%), received doses of tidutamab ranging from 0.1 to 2.0 mcg/kg. Dosing in the study included a lower priming dose, followed by a higher repeated dose on subsequent dosing days. The 20 patients in the expansion cohort received the recommended dosing regimen. Patients had a median age of 64 years and a median of four prior lines of systemic therapies. Fifty percent of patients received prior peptide receptor radionuclide therapy.

Tidutamab was generally well tolerated at the 0.3/1.0 mcg/kg dose identified for the expansion portion of the study. All 41 patients treated were included in the safety analysis. The most common treatment-related Grade 3 or Grade 4 adverse events across all doses were lymphopenia (29%), gamma-glutamyl transferase increases (20%), transaminase increases (20%) and vomiting (17%). In addition, Grade 3 esophageal dysmotility was observed in 7% of patients. CRS of any grade was observed in 41% of patients. The majority of CRS was limited to Grade 1 and Grade 2 and to the first two doses. Grade 3 CRS was observed in two patients (5%) upon the first dose. All patients experiencing CRS fully recovered.

Analysis of peripheral blood biomarkers indicated that tidutamab induced acute and sustained T-cell activation at the recommended dose for expansion. CD8-positive effector T cells showed a dose-dependent increase in proliferation (Ki67) and activation (PD-1) markers that began within 48 hours of the first dose and persisted at least seven weeks, as measured at cycle 2, day 22.

The best overall response was stable disease, with a disease control rate of 27%. Higher tumor PD-L1 expression was associated with a shorter time on study, and the patients with prolonged stable disease were most likely to have low or absent PD-L1 expression, suggesting a potential beneficial effect from the combination of tidutamab with PD-L1 inhibitors.

About Tidutamab

Tidutamab is a tumor-targeted bispecific antibody that contains both an SSTR2 binding domain and a T-cell binding domain (CD3). An XmAb bispecific Fc domain serves as the scaffold for the two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on tidutamab. SSTR2 (somatostatin receptor 2) is an antigen highly expressed on some solid tumors, and engagement of CD3 by tidutamab activates T cells for highly potent and targeted killing of SSTR2-expressing tumor cells. Tidutamab is being evaluated in an ongoing Phase 1b/2 study, which is enrolling patients with Merkel cell carcinoma and small cell lung cancer, SSTR2-expressing tumor types known to be responsive to immunotherapy.

On November 3, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported that the first patient has been dosed in the phase 1/2 GOBLET trial (Press release, Oncolytics Biotech, NOV 3, 2021, View Source [SID1234594292]). The trial is being managed by AIO, a leading academic cooperative medical oncology group based in Germany, and is designed to investigate the use of pelareorep in combination with Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab in patients with metastatic pancreatic, metastatic colorectal and advanced anal cancers.

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"Fewer than half of gastrointestinal (GI) cancer patients respond to immune checkpoint inhibitor (ICI) monotherapy, creating a pressing unmet need for techniques to enhance the efficacy of these agents," said Dirk Arnold M.D., Ph.D., Director of Asklepios Tumorzentrum Hamburg, and primary investigator of the GOBLET trial. "We believe that pelareorep can address this need and increase the proportion of GI cancer patients responding to ICIs, as clinical studies have shown that it reverses the immunosuppressive tumor microenvironments underlying checkpoint inhibitor resistance. Dosing the first patient in GOBLET represents a crucial step towards the evaluation of this hypothesis, and we look forward to the trial’s continued advancement."

The GOBLET study builds on data that was recently presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting that demonstrated clinical proof-of-concept for pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer (link to PR, link to poster). It is also supported by prior early clinical data showing that pelareorep-based combination treatments stimulated an adaptive immune response and led to a greater than 90% clinical benefit rate in KRAS-mutated colorectal cancer patients (link to PR, link to study) and a greater than 80% increase in progression-free survival in pancreatic cancer patients with low levels of CEACAM6 expression (link to PR, link to poster). In addition to evaluating the safety and efficacy of pelareorep-atezolizumab treatment, the trial also seeks to demonstrate the potential of CEACAM6 and T cell clonality as predictive biomarkers, which may allow selection of the most appropriate patients in future registration studies and increase their likelihood of success.

About GOBLET

The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication biomarker, safety, and efficacy study in advanced or metastatic gastrointestinal tumors. The study is being conducted at 15 centers in Germany. The primary endpoint of the study is safety, with overall response rate and biomarker evaluation (T cell clonality and CEACAM6) as exploratory endpoints. Approximately 55 patients are planned to be enrolled in four independent cohorts:

Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line metastatic pancreatic cancer patients (n=12);
Pelareorep in combination with atezolizumab in 1st line MSI (microsatellite instability)-high metastatic colorectal cancer patients (n=19);
Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients (n=14); and
Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients (n=10).
About AIO

AIO-Studien-gGmbH (AIO) emerged from the study center of the internal oncology working group within the German Cancer Society (DKG). AIO operates with a non-profit purpose of promoting science and research with a focus on internal oncology. Since its foundation, AIO has become a successful sponsor and study management company and has established itself both nationally and internationally.

About Gastrointestinal Cancer

Excluding skin cancers, colorectal cancer is the third most common cancer, with an estimated 104,270 new cases of colon cancer and 45,230 new cases of rectal cancer expected to be diagnosed in the U.S. in 20211. Also, for the 2021 year, the American Cancer Society estimates there will be 60,430 new cases of pancreatic cancer2 and 9,090 new cases of anal cancer3 in the U.S.

On November 3, 2021 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of drugs to treat severe metabolic, oncologic and neuropsychiatric disorders by modulating the effects of the hormone cortisol, reported its results for the quarter ended September 30, 2021 (Press release, Corcept Therapeutics, NOV 3, 2021, https://ir.corcept.com/news-releases/news-release-details/corcept-therapeutics-announces-third-quarter-financial-results-0 [SID1234594218]).

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Financial Results

Revenue of $96.1 million, an 11 percent increase from third quarter 2020
GAAP diluted net income of $0.24 per share, compared to $0.17 per share in third quarter 2020
Non-GAAP diluted net income of $0.30 per share, compared to $0.24 per share in third quarter 2020
Cash and investments of $495.2 million, compared to $471.6 million at June 30, 2021
Tightening of 2021 revenue guidance to $365 – $375 million
"The strong growth of our commercial business in the third quarter reflects the continued easing of COVID-related public health restrictions," said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. "Physicians are seeing their patients more frequently and, as a result, are better able to diagnose and treat patients with Cushing’s syndrome. As pandemic conditions recede, we expect our growth to continue. Korlym is an excellent treatment for Cushing’s syndrome and there are many eligible patients who have yet to receive it."

Corcept’s third quarter 2021 revenue was $96.1 million, compared to $86.3 million in the third quarter of 2020. Third quarter 2021 GAAP net income was $30.5 million, compared to $21.6 million in the third quarter of 2020. Excluding non-cash expenses related to stock-based compensation and the utilization of deferred tax assets, together with related income tax effects, non-GAAP net income in the third quarter was $37.0 million, compared to $30.0 million in the third quarter of 2020. A reconciliation of GAAP to non-GAAP net income is included below.

Corcept narrowed its 2021 revenue guidance to $365 – $375 million. The company’s previous guidance was $355 – $385 million.

Third quarter operating expenses were $59.9 million, compared to $61.6 million in the third quarter of 2020, primarily due to the conclusion of our studies in ovarian and pancreatic cancer, partially offset by increased employee compensation expenses, commercial spending and increased preclinical activities.

Cash and investments of $495.2 million at September 30, 2021 reflects the acquisition in the third quarter of $28.0 million of Corcept common stock – 1.2 million shares pursuant to the company’s stock repurchase program and 0.2 million shares in connection with the exercise of employee stock options. Over the term of the stock repurchase program, which began in November 2020, Corcept acquired 4.3 million shares of common stock at a cost of $98.2 million.

Clinical Development

"Cortisol modulation has the potential to help treat many serious diseases," said Dr. Belanoff. "Currently, our clinical programs are evaluating treatments for patients with solid tumors, non-alcoholic steatohepatitis (NASH), antipsychotic-induced weight gain (AIWG) and Cushing’s syndrome. We also continue to advance new cortisol modulators to the clinic. Early next year, we plan to start a Phase 2 trial in patients with amyotrophic lateral sclerosis (ALS)."

Solid Tumors

Phase 3 trial in patients with recurrent platinum-resistant ovarian cancer planned to start
in the first quarter of 2022; updated overall survival data from the Phase 2 trial expected in the first quarter of 2022
Selection of the optimum dose of exicorilant plus enzalutamide in patients with castration-resistant prostate cancer (CRPC) expected later this year
Enrollment continues in 20-patient, open-label, Phase 1b trial of relacorilant plus PD-1 checkpoint inhibitor pembrolizumab in patients with adrenal cancer with cortisol excess
"Leading gynecological oncologists have given us extremely positive feedback regarding the statistically significant and clinically meaningful results of our 178-patient, randomized, controlled Phase 2 trial in patients with recurrent platinum-resistant ovarian cancer and our plans to initiate a Phase 3 trial," said Bill Guyer, PharmD, Corcept’s Chief Development Officer. "We and our investigators are excited to advance relacorilant for the potential treatment of ovarian cancer and plan to meet with the FDA in the coming months to arrive at the best path forward."

Metabolic Diseases

Initiated Phase 1b dose-finding trial in patients with presumed NASH; results of our Phase 2 study to be presented at the American Association for the Study of Liver Diseases (AASLD) meeting, November 12 – 15
Completion of enrollment in GRATITUDE II, a 150-patient, double-blind, placebo-controlled Phase 2 trial of miricorilant to reverse long-standing AIWG, expected by year-end
Completion of enrollment in GRATITUDE, a 100-patient double-blind, placebo-controlled Phase 2 trial of miricorilant to reverse recent AIWG, expected by mid-2022
"At the AASLD meeting this month, we will present results from our Phase 2 trial, in which patients with presumed-NASH who received miricorilant experienced exceptionally large and rapid reductions in liver fat, accompanied by substantial, but transient, elevations of the liver enzymes ALT and AST," said Dr. Guyer. "Our hypothesis is that the rapidity and magnitude of miricorilant’s fat reducing effect irritated the liver. The objective of our Phase 1b study, initiated last month, is to identify a dosing regimen that can produce significant reductions in fat without causing liver irritation."

Cushing’s Syndrome

Enrollment continues in Phase 3 GRACE trial of relacorilant as a treatment for patients with all etiologies of Cushing’s syndrome; new drug application (NDA) submission expected in the second quarter of 2023
Enrollment continues in Phase 3 GRADIENT trial of relacorilant as a treatment for patients with Cushing’s syndrome caused by adrenal adenomas
"We expect our GRACE trial, which is accruing patients and generating data, to serve as the basis for relacorilant’s NDA in Cushing’s syndrome, and we are on track to make this submission in the second quarter of 2023," said Dr. Guyer. "The Phase 3 GRADIENT trial will produce valuable data about an etiology of Cushing’s syndrome that affects many patients, but has not been subject to rigorous, controlled study."

Conference Call

We will hold a conference call on November 3, 2021, at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time). To participate, Click this link (listen-only mode) or dial 1-833-693-0540 from the United States or 1-661-407-1581 internationally approximately 15 minutes before the start of the call. The passcode will be 5763926. A replay will be available on the Investors / Past Events tab of our website.

Hypercortisolism

Hypercortisolism, often referred to as Cushing’s syndrome, is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. In the United States, an estimated 20,000 patients have Cushing’s syndrome, with about 3,000 new patients diagnosed each year. Symptoms vary, but most patients experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Hypercortisolism can affect every organ system and can be lethal if not treated effectively. Corcept holds patents covering the composition of relacorilant and the use of cortisol modulators, including Korlym, in the treatment of patients with hypercortisolism.

On November 3, 2021 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported financial results for the third quarter ended September 30, 2021 (Press release, Zymeworks, NOV 3, 2021, View Source [SID1234594242]).

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"This year, we delivered upon our goal of presenting data showcasing the potential of zanidatamab to be the new foundational HER2-targeted therapy in first-line gastroesophageal adenocarcinoma (GEA)," said Ali Tehrani, Ph.D., Zymeworks’ President & CEO. "These data support the launch of our second pivotal study, HERIZON-GEA-01, and we look forward to continuing our recent clinical success with upcoming catalysts for zanidatamab in early- and late-line metastatic breast cancer as well as in combination with Ibrance, Tukysa, tislelizumab, and agents targeting the CD47 pathway."

Third Quarter 2021 Business Highlights and Recent Developments

Clinical Data Supports Zanidatamab as Potential New Standard of Care in 1L HER2+ GEA
In September, we presented Phase 2 clinical data for zanidatamab in combination with chemotherapy in first-line metastatic HER2-positive GEA at the European Society for Medical Oncology Annual Congress. The data support zanidatamab as a potential new standard of care in 1L HER2-positive GEA and the initiation of a global, randomized Phase 3 trial scheduled to launch in the fourth quarter of 2021. Further information relating to the pivotal trial design and commercial strategy in gastrointestinal cancers will be provided on a webcast on Tuesday, November 9, 2021 at 4:15 p.m. ET (1:15 p.m. PT). Interested parties can access a live webcast via Zymeworks’ website.
Zanidatamab Plus Chemotherapy in Late-Line Breast Cancer to be Presented at San Antonio Breast Cancer Symposium
The presentation will feature new clinical data for zanidatamab, in combination with chemotherapy, as a late-line treatment for patients with HER2-positive breast cancer. The presentation will be available on Wednesday, December 8, 2021.
First Patient Dosed in Clinical Trial of Zanidatamab and Anti-CD47 Evorpacept (ALX148)
The Phase 1b/2 clinical trial is designed to evaluate the safety and efficacy of zanidatamab in combination with ALX148 (anti-CD47) in patients with advanced HER2-positive breast cancer, HER2-low breast cancer, and additional non-breast HER2-expressing solid tumors.
Study Commences in Investigator-Initiated Trial of Zanidatamab as Neoadjuvant Treatment in HER2-Positive Breast Cancer
A Phase 2 open-label trial to evaluate zanidatamab monotherapy as neoadjuvant treatment in patients with newly diagnosed HER2-positive early breast cancer is being co-lead by Dr. Vincent Valero and Dr. Funda Meric-Bernstam at the University of Texas MD Anderson Cancer Center. The primary endpoint of this study is to assess efficacy by pathologic complete response.
ZW49 Program Update
The ZW49 program continues to advance in the weekly and once every three week dosing schedules. Expansion cohorts evaluating 2.5 mg/kg every three weeks have enrolled 29 patients and are expected to complete enrollment (30 patients) prior to year end. In parallel, the weekly dose regimen has enrolled 14 patients and continues to dose escalate as the maximum tolerable dose has not been reached. No dose-limiting toxicities have been observed to date. The results of these studies will inform the recommended Phase 2 dose and schedule with safety and efficacy data expected to be presented at a medical conference in 2022.
Financial Results for the Quarter Ended September 30, 2021

Zymeworks’ revenue relates primarily to non-recurring upfront fees, expansion payments or milestone payments from collaboration and license agreements, which can vary in timing and amount from period to period, as well as payments for research and development support. Revenue for the three months ended September 30, 2021 was $4.4 million compared to $2.6 million for the same period of 2020. Revenue for the third quarter of 2021 included a development milestone and research and development support under cost sharing arrangements. Revenue for the same period in 2020 included research and development support under cost sharing arrangements.

For the three months ended September 30, 2021, research and development expenses were $49.9 million compared to $54.4 million for the same period of 2020. The decrease was primarily due to lower third-party manufacturing expenses for zanidatamab which were partially offset by higher salary and benefit expenses from additional headcount as well as higher preclinical and other research and development program expenses. For the three months ended September 30, 2021, research and development expenses included non-cash stock-based compensation expense of $5.6 million from equity-classified equity awards and a $1.0 million recovery from the non-cash mark-to-market revaluation of certain historical liability-classified equity awards. Excluding stock-based compensation, research and development expenses decreased by $3.3 million for the three months ended September 30, 2021 compared to the same period in 2020.

For the three months ended September 30, 2021, general and administrative expenses were $15.5 million compared to $21.9 million for the same period in 2020. For the three months ended September 30, 2021, general and administrative expenses included non-cash stock-based compensation expense of $4.8 million from equity-classified equity awards and a $3.6 million recovery from the non-cash mark-to-market revaluation of certain historical liability-classified equity awards. Excluding stock-based compensation, general and administrative expenses increased by $4.9 million for the three months ended September 30, 2021 compared to the same period in 2020 primarily due to higher salary and benefit expenses from additional headcount, and professional fees.

Net loss for the three months ended September 30, 2021 was $60.6 million compared to $72.6 million for the same period of 2020. This was primarily due to the decrease in research and development and general and administrative expenses and the increase in revenue referred to above, which was partially offset by a decrease in interest income.

Zymeworks expects research and development expenditures to increase over time in line with the advancement and expansion of the Company’s clinical development of its product candidates, as well as its ongoing preclinical research activities. Additionally, Zymeworks anticipates continuing to receive revenue from its existing and future strategic partnerships, including technology access fees and milestone-based payments. However, Zymeworks’ ability to receive these payments is dependent upon either Zymeworks or its collaborators successfully completing specified research and development activities.

As of September 30, 2021, Zymeworks had $307.8 million in cash resources consisting of cash, cash equivalents and short-term investments. Based on our current operating plan, we believe that our current cash resources, combined with the collaboration payments we anticipate receiving, will enable us to fund our planned operations into late 2022 and potentially beyond.

On November 3, 2021 Ascendis Pharma A/S (Nasdaq: ASND), reported that the Company will hold a conference call and live webcast on Wednesday, November 10, 2021 at 4:30 p.m. Eastern Time (ET) to review its third quarter 2021 financial results and provide a business update (Press release, Ascendis Pharma, NOV 3, 2021, View Source [SID1234594258]).

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Conference Call Details

A live webcast of the conference call will be available on the Investors and News section of the Ascendis Pharma website at www.ascendispharma.com. A webcast replay will be available on this website shortly after conclusion of the event for 30 days.