On February 23, 2022  Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported a corporate update and reported financial results for the quarter and year ended December 31, 2021 (Press release, Allogene, FEB 23, 2022, View Source [SID1234608889]).

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"The FDA hold placed upon our clinical programs presented us with an unexpected challenge during the fourth quarter. In responding to and resolving this challenge, our team continued to demonstrate the qualities of leadership, collaboration, innovation, and focus that are required to be a pioneer in the field of allogeneic T cell therapy. I am incredibly proud of our employees’ commitment and relentless belief in the potential for our products to improve the lives of patients," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "Our mission has been, and continues to be, the first to bring allogeneic CAR T products to the market in blood cancers and solid tumors. We believe we are on track and have what it takes to execute on this vision and look forward to advancing our broad portfolio of product candidates."

Corporate Highlights
On January 10, 2022, Allogene announced that the U.S. Food and Drug Administration (FDA) had removed the clinical hold on all AlloCAR T clinical trials which was announced on October 7, 2021. After extensive investigation by Allogene, it was determined that the chromosomal abnormality detected in a single patient treated with ALLO-501A was unrelated to TALEN gene editing or Allogene’s manufacturing process and had no clinical significance. The abnormality was not detected in any manufactured AlloCAR T product or in any other patient treated with the same ALLO-501A lot. The abnormality occurred after the cell product was administered and involved regions of the T cell receptor and immunoglobulin genes known to undergo rearrangement as part of the T cell or B cell maturation process.

Allogene has resumed clinical study activities on ALLO-715 and ALLO-605 for relapsed/refractory (R/R) multiple myeloma (MM), and ALLO-316 for advanced or metastatic clear cell renal cell carcinoma (RCC), and began enrolling patients earlier this month. Enrollment in the Phase 1 ALLO-501 ALPHA trial in R/R non-Hodgkin lymphoma (NHL) has completed accrual. The focus remains on preparing for the pivotal Phase 2 ALPHA2 trial of ALLO-501A in R/R Large B Cell Lymphoma (LBCL). Prior to the start of Phase 2, Allogene plans to resume enrollment in the Phase 1 study in order to offer AlloCAR T to patients in need.

Cell Forge 1 (CF1)
CF1, Allogene’s state-of-the-art manufacturing facility located in Newark, California is now fully operational and producing GMP material with the intent of supplying ALLO-501A for the planned pivotal study.

Pipeline Updates

Anti-CD19 Program
Phase 1 data from the ALPHA trial with ALLO-501 and ALPHA2 trial with ALLO-501A for the treatment of R/R NHL was presented at the 2021 Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Data from these trials continue to support the promise of Allogene’s platform to provide a safe and durable alternative to approved autologous CAR T therapies in CAR T naïve patients.

Highlights from the ASH (Free ASH Whitepaper) 2021 presentation include:

AlloCAR T was associated with consistent and manageable safety with no dose limiting toxicities (DLTs) or graft-vs-host disease (GvHD) and minimal Grade 3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), or Grade 3 cytokine release syndrome (CRS).
There were no relapses observed in LBCL CAR T naïve patients across trials who had achieved a complete response (CR) at six months with the longest ongoing CRs with ALLO-501 at 18+ months and ALLO-501A at 15+ months.
One of the most critical advantages of AlloCAR T was further established with more than 97% of enrolled patients able to receive therapy with the median time from enrollment to initiation of treatment of five days in ALPHA and two days in ALPHA2.
Phase 2 Preparation:
The single-arm ALPHA2 trial is on track to begin mid-year 2022 with FDA discussions directed at finalizing clinical trial design and proactively accelerating activities that address Chemistry Manufacturing and Controls (CMC) requirements.

Allogene is developing ALLO-647, its proprietary anti-CD52 monoclonal antibody intended to enable expansion and persistence of AlloCAR T product candidates, including ALLO-501A. Allogene intends to launch a separate registrational trial for ALLO-647 at the time of the pivotal Phase 2 trial for ALLO-501A as part of the concurrent development plan. This trial is intended to demonstrate the safety of ALLO-647 along with its contribution to the overall benefit of the lymphodepletion regimen.

Anti-BCMA AlloCAR T Program
Allogene’s anti-BCMA strategy includes the Phase 1 UNIVERSAL trial, which has cohorts evaluating ALLO-715 as a monotherapy, consolidated dosing of ALLO-715 using ALLO-647 to selectively extend the window of lymphodepletion, and ALLO-715 in combination with SpringWorks Therapeutics’ investigational gamma secretase inhibitor, nirogacestat. The Phase 1 IGNITE trial is evaluating ALLO-605, Allogene’s first TurboCAR candidate. TurboCAR technology allows cytokine activation signaling to be engineered selectively into CAR T cells and has shown the ability to improve the potency and persistence of allogeneic cells in preclinical models. Activity in these trials has resumed and Allogene intends to provide a BCMA program clinical update by the end of 2022.

ALLO-715 UNIVERSAL Trial
Data from the UNIVERSAL trial with ALLO-715 as a monotherapy for the treatment of R/R MM was also presented at ASH (Free ASH Whitepaper) 2021. The UNIVERSAL trial is the first allogeneic anti-BCMA CAR T to demonstrate safety and substantial efficacy in MM with response rates that are similar to the approved autologous CAR T therapy.

The data presented at ASH (Free ASH Whitepaper) demonstrated that ALLO-715 was well tolerated with no GvHD and a manageable safety profile.
There was a 71% Overall Response Rate (ORR) at dose level 3 (320 million AlloCAR T+ cells) with lymphodepletion consisting of fludarabine/cyclophosphamide and ALLO-647
46% of patients achieved a Very Good Partial Response or better (VGPR+) including 25% Complete Response or Stringent Complete Response (CR/sCR).
92% of patients with VGPR+ were minimal residual disease (MRD) negative.
Median duration of response (DoR) was 8.3 months at the time of data cut-off.
Importantly, the study highlighted the ability to initiate treatment within five days of enrollment and eliminate the need for bridging therapy.
Solid Tumor AlloCAR T Program

ALLO-316 (anti-CD70) – TRAVERSE Trial

The Phase 1 trial for Allogene’s first AlloCAR T candidate for solid tumors, ALLO-316, is designed to evaluate the safety, tolerability, anti-tumor efficacy, pharmacokinetics, and pharmacodynamics of ALLO-316 in patients with advanced or metastatic clear cell RCC. Clinical trial activities have resumed.
Fourth Quarter and Year-End Financial Results

Research and development expenses were $54.0 million for the fourth quarter of 2021, which includes $11.1 million of non-cash stock-based compensation expense. For the full year of 2021, research and development expenses were $220.2 million. Research and development expense for the year includes $39.6 million of non-cash stock-based compensation expense.
General and administrative expenses were $20.0 million for the fourth quarter of 2021, which includes $10.9 million of non-cash stock-based compensation expense. For the full year of 2021, general and administrative expenses were $74.1 million, which includes $41.2 million of non-cash stock-based compensation expense.
Net loss for the fourth quarter of 2021 was $74.9 million, or $0.54 per share, including non-cash stock-based compensation expense of $22.0 million. For the full year of 2021, net loss was $257.0 million, or $1.89 per share, including non-cash stock-based compensation expense of $80.8 million.
The Company had $810 million in cash, cash equivalents, and investments as of December 31, 2021.
2022 Financial Guidance

Allogene expects full year GAAP Operating Expenses to be between $360 million and $390 million including estimated non-cash stock-based compensation expense of $90 million to $100 million and excluding any impact from potential business development activities.
Conference Call and Webcast Details
Allogene will host a live conference call and webcast today at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss financial results and provide a business update. To access the live conference call by telephone, please dial 1 (866) 940-5062 (U.S.) or 1 (409) 216-0618 (International). The conference ID number for the live call is 4973864. The webcast will be made available on the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.

On February 23, 2022 Dynavax Technologies Corporation (Nasdaq: DVAX), a biopharmaceutical company focused on developing and commercializing vaccines, reported that Ryan Spencer, Chief Executive Officer and Kelly MacDonald Chief Financial Officer, will participate in a virtual fireside chat at the Cowen 42nd Annual Health Care Conference on Wednesday, March 9, at 2:50 p.m. E.T (Press release, Dynavax Technologies, FEB 23, 2022, https://investors.dynavax.com/news-releases/news-release-details/dynavax-present-cowen-42nd-annual-health-care-conference [SID1234608888]).

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The presentation will be webcast and may be accessed through the "Events & Presentations" page on the "investors" section of the Company’s website at View Source

On February 23, 2022 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported financial results for the fourth quarter and full year ended December 31, 2021 and provided a review of recent business and clinical highlights (Press release, Xencor, FEB 23, 2022, View Source [SID1234608887]).

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"In 2021, we made significant decisions to advance our portfolio of internal XmAb drug candidates — the initiation of Phase 2 trials in prostate cancer with vudalimab, the entry into our second collaboration with Janssen, focused on plamotamab and additional CD28 bispecifics, as well as the decision to stop a Phase 1 program, vibecotamab. We are focused on using our resources on the most promising clinical-stage programs and on the next wave of additional reduced-potency cytokines, CD28 T cell engagers and 2+1 CD3 T cell engagers," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "We also maintained a strong financial position to support our portfolio, receiving over $200 million in collaboration upfront and milestone payments, as well as royalties from the first three XmAb medicines now marketed by our partners."

Dr. Dahiyat continued, "Looking ahead, in 2022, we expect to present additional clinical data from our mid-stage development programs and initiate new studies for vudalimab and plamotamab. Also, we soon expect to initiate a Phase 1 study for XmAb819, our ENPP3 x CD3 bispecific antibody for renal cell carcinoma, which was engineered with our multivalent 2+1 format for greater tumor selectivity, an especially valuable tool for accessing challenging solid tumor antigens. We also plan to initiate new clinical trials for our lead cytokine, XmAb306, and to report data and initiate a new clinical study for our second engineered cytokine program, XmAb564. We remain excited by additional opportunities, both internally and together with our partners, to use our technologies and protein engineering capabilities to address challenging areas of biology and continually grow our portfolio."

Recent Portfolio Highlights

Vudalimab (PD-1 x CTLA-4): In November 2021, Xencor presented updated expansion cohort data from the Phase 1 study of vudalimab in patients with multiple types of advanced solid tumors at the SITC (Free SITC Whitepaper) Annual Meeting. The results from the study indicate vudalimab was generally well tolerated and demonstrated activity in advanced prostate cancer, ovarian cancer, and multiple other tumor types and have informed Phase 2 development plans. The Company is currently enrolling a Phase 2 study in patients with metastatic castration-resistant prostate cancer (mCRPC), where vudalimab is being evaluated as a monotherapy or in combination with chemotherapy or a PARP inhibitor depending on the tumor’s molecular subtype. The Company plans to present initial data from the study in the second half of 2022. A second Phase 2 study will begin this year, evaluating vudalimab monotherapy in patients with advanced pelvic tumors, including clinically defined high-risk mCRPC and certain gynecologic malignancies.
Plamotamab (CD20 x CD3): In December 2021, Xencor presented updated dose-escalation data from the Phase 1 study of plamotamab at the ASH (Free ASH Whitepaper) Annual Meeting. Expansion cohorts are actively recruiting patients with DLBCL and FL and are dosing using the recommended Phase 2 regimen to further evaluate the safety and efficacy of plamotamab monotherapy. In 2022, subcutaneous administration of plamotamab will be incorporated into the study, and the Company plans to present data from the expansion cohorts in the second half of the year. The Company is currently opening clinical sites for the potentially registration-enabling Phase 2 study, evaluating plamotamab in combination with tafasitamab and lenalidomide, in patients with relapsed or refractory DLBCL.
XmAb564 (IL2-Fc): XmAb564 is a potency-reduced IL2-Fc fusion protein targeting regulatory T cells, and it is being developed for patients with autoimmune disease. Xencor is conducting a Phase 1 study to evaluate the safety and tolerability of a single dose of XmAb564, administered subcutaneously in healthy adult volunteers. The Company plans to present tolerability, durability and biomarker data from the study in 2022 and plans to initiate a multiple-ascending dose study in select patient populations.
XmAb306 (IL15/IL15Rα-Fc): XmAb306 is a potency-reduced IL15/IL15Rα-Fc fusion protein targeting NK and T cells for the treatment of patients with cancer, which Xencor is co-developing with Genentech, a member of the Roche Group. In November 2021, Xencor announced that XmAb306 promoted high levels of sustained NK cell expansion and evidence of peripheral effector T cell proliferation, in an ongoing Phase 1 dose-escalation study of XmAb306 in patients with advanced solid tumors. Additional studies of XmAb306 in combination with other therapeutic agents are being planned.
Preclinical Data Presentations: New data from four preclinical-stage programs, including Xencor’s IL-12-Fc cytokine program (XmAb662), PD-L1 x CD28 bispecific antibody program, TGFβR2 bispecific antibody platform, and bispecific NK cell engager platform, were presented at the SITC (Free SITC Whitepaper) Annual Meeting.
Progress Across Partnered Programs and New Partnerships

Vir Biotechnology, Inc.: In 2021, Xencor recognized $52.2 million in royalty revenue under the Company’s agreement with Vir. Sotrovimab, an antibody that targets the SARS-CoV-2 virus and incorporates Xencor’s Xtend Fc domain for longer duration of action, is made available by Vir and its partner Glaxo Wellcome UK Limited and GlaxoSmithKline Biologicals S.A. under an emergency use authorization (EUA) from the U.S. FDA for the treatment of mild-to-moderate COVID-19 in high-risk adults and pediatric patients. Sotrovimab has also been granted a marketing authorization in the European Union, approved via Japan’s Special Approval for Emergency Pathway in Japan, and granted conditional, provisional, or temporary authorizations for the early treatment of COVID in 15 other countries.
Janssen Biotech, Inc.: In the fourth quarter of 2021, Janssen selected a CD28 bispecific antibody candidate under the November 2020 collaboration agreement, and the Company earned a $5.0 million milestone payment. The first collaboration between Janssen and Xencor is focused on the discovery of XmAb bispecific antibodies against CD28, an immune co-stimulatory receptor on T cells, and an undisclosed prostate tumor target, for the potential treatment of patients with prostate cancer. Under the agreement, the Company has a right to access select, predefined agents from Janssen’s portfolio of clinical-stage drug candidates and commercialized medicines to evaluate potential combination therapies in prostate cancer with agents in the Company’s own pipeline, subject to some limitations. Janssen has the same right with Xencor’s portfolio to evaluate potential combination therapies in prostate cancer.
Amgen Inc.: Amgen is enrolling patients with mCRPC in a Phase 1 study evaluating AMG 509 (STEAP1 x CD3), an XmAb 2+1 bispecific antibody. The XmAb 2+1 multivalent format enables higher binding capability for STEAP1 expressing cells. In February 2022, Amgen presented encouraging, preliminary data highlighting AMG 509’s pharmacodynamic activity of maximum prostate specific antigen (PSA) decline among 30 patients in the study, which provides an early signal of activity and potential validation for the capabilities of the XmAb 2+1 bispecific antibody format.
Zenas BioPharma Ltd.: In November 2021, Xencor entered into a second product license agreement with Zenas and granted Zenas the exclusive worldwide rights to develop and commercialize obexelimab, which uses the XmAb Immune Inhibitor Fc Domain and targets CD19 with its variable domains, to inhibit the function of B cells. Xencor received a warrant to acquire additional equity in Zenas and is eligible to receive up to $470 million in milestone payments and tiered, mid-single digit to mid-teen percent royalties upon commercialization of obexelimab, dependent on geography.
Financial Results for the Fourth Quarter and Full Year Ended December 31, 2021

Cash, cash equivalents, receivables and marketable debt securities totaled $664.1 million as of December 31, 2021, compared to $610.2 million on December 31, 2020. During 2021, the Company received upfront payments, milestone payments and royalties from partners of $204.9 million, which offset spending on operations and resulted in an increase in the year-end cash balance.

Revenues for the fourth quarter ended December 31, 2021 were $154.0 million, compared to $41.9 million for the same period in 2020. Revenues for full year 2021 were $275.1 million, compared to $122.7 million in 2020. Total revenues earned in 2021 included revenues earned from Xencor’s Janssen and Novartis collaborations and royalties from the Alexion, Vir and MorphoSys agreements, compared to revenue earned from royalties and milestones from the MorphoSys and Alexion agreements and the licensing of XmAb technologies and drug candidates in 2020.

Research and development expenses for the fourth quarter ended December 31, 2021 were $51.0 million, compared to $47.9 million for the same period in 2020. Research and development expenses were $192.5 million for the full year ended December 31, 2021, compared to $169.8 million in 2020. Increased research and development spending for full year ended December 31, 2021 compared to 2020 reflects increased spending on XmAb819 (ENPP3 x CD3) and other early-stage programs, including XmAb808 (B7-H3 x CD28) and XmAb662 (IL-12).

General and administrative expenses for the fourth quarter ended December 31, 2021 were $11.4 million, compared to $7.6 million in the same period in 2020. General and administrative expenses were $38.8 million in the full year 2021, compared to $29.7 million in 2020. Increased general and administrative spending for the full year ended December 31, 2021 compared to 2020 reflects increased staffing, facility costs and additional spending on professional services, including intellectual property costs and licensing fees.

Non-cash, share based compensation expense for the year ended December 31, 2021 was $37.0 million, compared to $31.6 million for the year ended December 31, 2020.

Net income for the fourth quarter ended December 31, 2021 was $73.1 million, or $1.21 on a fully diluted per share basis, compared to a net loss of $13.7 million, or $(0.24) on a fully diluted per share basis, for the same period in 2020. For the full year ended December 31, 2021, net income was $82.6 million, or $1.37 on a fully diluted per share basis, compared to a net loss of $69.3 million, or $(1.21) on a fully diluted per share basis, for the full year ended December 31, 2020. Higher net income reported for 2021 compared to 2020 is primarily due to increased royalties and revenue recognized from collaborations in 2021.

The total shares outstanding were 59,355,558 as of December 31, 2021, compared to 57,873,444 as of December 31, 2020.

Financial Guidance

Based on current operating plans, Xencor expects to have cash to fund research and development programs and operations through the end of 2025. Xencor expects to end 2022 with between $500 million and $550 million in cash, cash equivalents, receivables and marketable debt securities.

Conference Call and Webcast

Xencor will host a conference call today at 4:30 p.m. ET (1:30 p.m. PT) to discuss full year 2021 financial results and provide a corporate update.

The live call may be accessed by dialing (877) 359-9508 for domestic callers or +1 (224) 357-2393 for international callers and referencing conference ID number 5290676. A live webcast of the conference call will be available online from the Investors section of the Company’s website at www.xencor.com. The webcast will be archived on the company’s website for 30 days.

On February 23, 2022 Nascent Biotech, Inc. (OTCQB: NBIO) ("Nascent Biotech", "Nascent", or the "Company"), a clinical-stage biotechnology Company pioneering the development of monoclonal antibodies targeting treatment of various cancers and viral infections, reported that the Company has received a payment totaling USD $750,000 from BioRay Pharmaceutical, Ltd. ("BioRay") in association with the Licensing Agreement established between the two companies in May 2021 (Press release, Nascent Biotech, FEB 23, 2022, View Source [SID1234608886]). This payment represents the Second Payment stipulated in the Licensing Agreement (the "Agreement").

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The Agreement grants to BioRay exclusive rights to commercialize Nascent’s monoclonal antibody, Pritumumab, in international markets, excluding North America and Central America. Under terms of the Agreement, Nascent will receive a total of USD $5,000,000 to be paid out at various stipulated milestones. The initial payment of USD $1,000,000 was received by Nascent on April 20, 2021.

This second payment of USD $750,000 was received by Nascent for entering the third cohort in Nascent’s first Phase 1 clinical trial of Pritumumab.

A third payment of USD $2,500,000 will be received by Nascent upon approval from the FDA to conduct a Phase 2 clinical trial of Pritumumab. The final USD $750,000 payment will be received by Nascent upon the commencement of the Phase 2 clinical trial.

"There continue to be significant unmet medical needs across a variety of cancers," remarked Sean Carrick, CEO of Nascent Biotech. "We are highly encouraged by Pritumumab’s potential as an innovative, first-in-class treatment candidate, and we are delighted to be working closely with BioRay in this collaboration."

On February 23, 2022 Nichi-Iko Pharmaceutical Co., Ltd. has recently reported that it received approval for a biosimilar of bevacizumab BS intravenous infusion 100 mg/400 mg, whose marketing authorization application was filed based on the clinical pharmacokinetic (PK) study data conducted in Japan in addition to the global Phase 3 study data conducted by mAbxience (Press release, mAbxience, FEB 23, 2022, View Source [SID1234608885]).

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Bevacizumab BS is highly similar to the reference medicinal product and data has shown a comparable quality, safety and efficacy to Avastin. Bevacizumab BS is indicated for the treatment of advanced or recurrent colorectal cancer that is not curatively resectable and advanced or recurrent non-small cell lung cancer that is not resectable except for squamous cell carcinoma.