On November 8, 2021 GeneCentric Therapeutics, a company making precision medicine more precise through RNA-based diagnostics, reported the closing of an oversubscribed Series B1 financing, which raised $7.5 million (Press release, GeneCentric Therapeutics, NOV 8, 2021, View Source [SID1234594674]).

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Proceeds will be used to commercialize GeneCentric’s gene signatures and accelerate the growth of its pipeline of predictive response signatures for oncology therapeutics. New investors include IAG Capital Partners and Alexandria Venture Investments, along with existing investors Labcorp and Hatteras Venture Partners.

"This financial support from our investors demonstrates the continued enthusiasm for RNA-based diagnostics and genomic tools as a means to accelerate the development of new cancer therapeutics," said Mike Milburn, PhD, president and CEO of GeneCentric Therapeutics. "This is an exciting time for GeneCentric as we deploy our growing pipeline of RNA-based genomic analysis solutions across multiple tumor types and therapeutic options."

In addition to developing its signature and diagnostic pipeline, GeneCentric will continue to pursue key pharmaceutical and biotechnology collaborations where its core technologies can be used to advance new and ongoing partner programs.

About the rT(I)ME Explorer Platform

GeneCentric’s broad pipeline of novel predictive response signatures has been built over the past decade using its proprietary RNA-based Tumor and Immune Micro-Environment (rT(I)ME) Explorer bioinformatics platform. These RNA-based response signatures allow for improved patient selection for new and existing targeted and immune oncology therapeutics, as well as expansion into new tumor types. The rT(I)ME Explorer platform also allows for deeper insight into rational combination strategies, as there is increased interest in combining small molecule-targeted therapies with immuno-oncology agents or use of multiple immuno-oncology agents. By applying its rT(I)ME Explorer technology, GeneCentric is expanding drug response biomarkers and identifying new targets to enable more effective and efficient drug development.

On November 8, 2021 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported financial results for the third quarter ended September 30, 2021 and provided an update on the ARC-7 study of domvanalimab (Press release, Arcus Biosciences, NOV 8, 2021, View Source [SID1234594702]). Gilead Sciences has initiated its opt-in review process to potentially obtain rights to the Arcus anti-TIGIT program. If the option is exercised and closed, Gilead would obtain rights to both domvanalimab and AB308, a second and differentiated anti-TIGIT antibody in the Arcus portfolio. A decision is expected prior to the end of 2021.

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"The initiation of Gilead’s opt-in review process for our anti-TIGIT program is an important step towards our shared commitment to develop differentiated combination therapies for people with cancer," said Terry Rosen, Ph.D., Chief Executive Officer of Arcus. "We expect to continue our strong momentum of significant program advancement and milestone achievement starting with an update this fall from our Phase 1 study of quemliclustat, our first-in-class small molecule CD73 inhibitor, in development for pancreatic cancer, an area of enormous unmet need. Quemliclustat is a central component of our late-stage development strategy for 2022 and beyond."

Corporate & Partnership Updates

Gilead initiated the opt-in review process for our anti-TIGIT program. A decision is expected prior to the end of 2021. If Gilead exercises its option, and subject to receipt of applicable anti-trust approvals:
Arcus would receive a $275 million opt-in payment, and the parties would co-develop and share equally the global development costs related to the anti-TIGIT program.
Gilead would obtain rights to both domvanalimab, our Fc-silent anti-TIGIT antibody currently being evaluated in Phase 2 and Phase 3 studies, and AB308, our Fc-enabled anti-TIGIT antibody currently in a Phase 1 study in advanced malignancies.
If approved, Arcus and Gilead would co-commercialize and equally share profits and losses to both anti-TIGIT antibodies in the United States. Gilead would receive exclusive rights outside the U.S., subject to any rights of Arcus’s existing partners, and Gilead would pay to Arcus tiered royalties ranging from the high teens to low twenties.
Our collaboration partner Taiho initiated a Phase 1 platform study evaluating zimberelimab (our anti-PD1 antibody) with Taiho’s intra-portfolio combinations targeting oncology indications. The TARP (Taiho-Arcus Platform) study is currently enrolling. Further details can be found at View Source Trial Identifier: NCT04999761.
Zimberelimab was approved in China as a second-line treatment for recurrent/refractory classical Hodgkin lymphoma (CHL); Gloria Biosciences holds all rights to zimberelimab in China and conducts its development of zimberelimab independent of Arcus’s activities.
Anti-TIGIT program

Recent Highlights

Arcus conducted a second interim analysis (IA2) for ARC-7, our open-label randomized Phase 2 study evaluating the safety and efficacy of domvanalimab plus zimberelimab vs. zimberelimab alone vs. domvanalimab plus zimberelimab and etrumadenant (dual adenosine A2a/A2b receptor antagonist) as a first-line treatment for PD-L1 ≥ 50% and EGFR/ALK wild-type, metastatic NSCLC. The study has a target total enrollment of 150 patients who are being randomized 1:1:1 across three study arms and treated until disease progression or loss of clinical benefit. The timing of this interim analysis was pre-specified in the protocol to occur when a certain number of patients were randomized and had at least two disease evaluations.
Summary of Efficacy Observations from IA2:

Both domvanalimab-containing arms demonstrated differentiated clinical activity compared to that of zimberelimab alone.
Zimberelimab alone continued to demonstrate activity similar to that of other marketed anti-PD-1 antibodies in the setting.
As expected with immunotherapy treatments, continued deepening of response and greater tumor shrinkage were observed in patients with longer follow-up in both domvanalimab-containing arms.
Since the previous interim analysis, the doublet continued to show encouraging activity relative to the monotherapy, and the triplet continued to numerically outperform the doublet.
As of the data cut-off date for this interim analysis, data for progression-free survival (PFS) was immature but indicated that fewer events of progression or death had occurred in the domvanalimab-containing arms compared to zimberelimab alone.
Summary of Safety Observations from IA2:

No unexpected safety signals were observed; the current safety profile for each molecule in the study appeared to be consistent with known and published immune checkpoint inhibitors in this setting.
Early safety data from this interim analysis showed a lower incidence of infusion reactions relative to published numbers from other anti-TIGIT plus anti-PD-(L)1 clinical studies.
Arcus initiated enrollment of five expansion cohorts in the Phase 1b portion of the ARC-12 study evaluating AB308 plus zimberelimab in advanced malignancies. This study is designed to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of AB308 plus zimberelimab in tumor types believed to be potentially responsive to anti-TIGIT antibodies.
Upcoming anti-TIGIT Milestones:

ARC-7 is expected to be fully enrolled by mid-2022, and we anticipate a data presentation later in 2022, which will include progression-free survival data.
ARC-10, an ongoing registrational Phase 3 study in first-line, locally advanced or metastatic PD-L1≥50% NSCLC, continues to enroll and, if positive, is intended to support the potential approvals of both zimberelimab monotherapy and domvanalimab plus zimberelimab.
AstraZeneca and Arcus remain on track to initiate the PACIFIC-8 registrational Phase 3 study to evaluate domvanalimab plus durvalumab, an anti-PD-L1 antibody, in unresectable Stage 3 NSCLC with curative intent, where durvalumab is standard of care, by the end of 2021.
We are planning several additional clinical studies of domvanalimab-based combinations, including two additional Phase 3 studies anticipated to start in mid-2022.
Quemliclustat (small molecule anti-CD73 inhibitor)

Upcoming Milestones:

An update on ARC-8, our Phase I study of quemliclustat plus zimberelimab and gemcitabine/nab-paclitaxel in first-line metastatic pancreatic ductal adenocarcinoma (PDAC), is planned for this fall. This update includes data on approximately 30 patients treated at the 100mg and 125mg dose of quemliclustat.
We expect the randomized portion of ARC-8 to complete enrollment by the end of this month. This 90-patient cohort is evaluating quemliclustat plus zimberelimab and gemcitabine/nab-paclitaxel vs. quemliclustat plus gemcitabine/nab-paclitaxel to determine whether zimberelimab adds clinical benefit to the combination.
We anticipate landmark six-month PFS data from the randomized portion of ARC-8 in mid-2022. These results will inform the design of our planned Phase 3 study with the goal of starting this first registrational study for quemliclustat in 2022.
Etrumadenant (A2a/A2b adenosine receptor antagonist)

Upcoming Milestones:

ARC-4, our randomized Phase 1b study in EGFR+ NSCLC: we expect initial randomized data, including overall response rates and PFS, to be presented in 1H22. ARC-4 is evaluating etrumadenant plus zimberelimab and chemotherapy vs. zimberelimab plus chemotherapy in EGFRmut tyrosine kinase inhibitor (TKI)-relapsed and refractory NSCLC.
ARC-6, our Phase 1b/2 platform study in metastatic castration-resistant prostate cancer: we anticipate initial results in 2022 from the randomized cohort that is evaluating docetaxel versus docetaxel plus etrumadenant and zimberelimab.
Discovery Programs:

Upcoming Milestones:

AB308 (Fc-enabled anti-TIGIT antibody) poster presentation at the 2021 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting, November 10-14, 2021.
Poster #258, Title: AB308 is an Anti-TIGIT Antibody That Enhances Immune Activation and Anti-tumor Immunity Alone and in Combination with Other I-O Therapeutic Agents.
AB521 (HIF-2α inhibitor): we expect to initiate Phase 1 clinical development in the fourth quarter of 2021. This first study is in healthy volunteers and is designed to expeditiously characterize the pharmacokinetic and safety profile of AB521 and to identify the starting dose for the planned Phase 1/1b study in oncology patients.
Financial Results for the Third Quarter 2021

Cash, cash equivalents and investments were $743.4 million as of September 30, 2021, compared to $735.1 million as of December 31, 2020. The increase was primarily due to gross proceeds of $220.4 million received upon the closing of the private placement of common stock under the Amended and Restated Stock Purchase Agreement with Gilead in February 2021, partially offset by cash utilized for our operations. We expect cash, cash equivalents and marketable securities on hand to be sufficient to fund operations at least through 2023.
Revenues: Collaboration and license revenues were $9.5 million for the three months ended September 30, 2021, compared to $64.5 million for the same period in 2020. In the three months ended September 30, 2021, we recognized $7.7 million in collaboration revenue related to Gilead’s ongoing rights to access our research and development pipeline in accordance with the Gilead collaboration agreement, as well as $1.8 million related to the Taiho collaboration agreement. In the three months ended September 30, 2020, we recognized $55.1 million in revenue related to Gilead’s license to zimberelimab and $7.7 million in collaboration revenue related to their access to our research and development pipeline, as well as $1.8 million related to the Taiho collaboration agreement. Collaboration and license revenues were $28.4 million for the nine months ended September 30, 2021, compared to $68.0 million for the same period in 2020.
R&D Expenses: Research and development expenses were $71.3 million for the three months ended September 30, 2021, compared to $51.8 million for the same period in 2020. The increase was primarily driven by costs incurred to support our expanded clinical and development activities including increased compensation costs related to a larger employee base, increased clinical trial costs, and increased early-stage research costs. Approximately $4.9 million of the increase in compensation costs is related to non-cash stock-based compensation. The overall increase in research and development expenses is partially offset by a decrease in milestone expenses incurred. Research and development expenses were $206.4 million for the nine months ended September 30, 2021, compared to $110.6 million for the same period in 2020.
G&A Expenses: General and administrative expenses were $16.3 million for the three months ended September 30, 2021, compared to $11.2 million for the same period in 2020. The increase was driven by the increased complexity of supporting our expanding clinical pipeline and collaboration obligations, as well as compliance costs associated with our growth. Our growing employee base and 2021 stock awards drove an increase in employee compensation costs, including approximately $3.7 million of increased non-cash stock-based compensation. The overall increase was partially offset by decreases in legal, accounting and consulting expenses due to costs related to the transaction with Gilead and other corporate development activities incurred in 2020. General and administrative expenses were $49.0 million for the nine months ended September 30, 2021, compared to $29.6 million for the same period in 2020.
Net Loss: Net loss was $78.0 million for the three months ended September 30, 2021, compared to net income of $1.8 million for the same period in the prior year. Net loss was $226.5 million for the nine months ended September 30, 2021, compared to $71.0 million for the same period in 2020.

Carbo/pem: carboplatin/pemetrexed; dom: domvanalimab; durva: durvalumab; etruma: etrumadenant; gem/nab-pac: gemcitabine/nab-paclitaxel; quemli: quemliclustat; SOC: standard of care; zim: zimberelimab CRC: colorectal cancer; CRPC: castrate-resistant prostate cancer; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma

About domvanalimab and AB308

Domvanalimab, Arcus’s most advanced anti-TIGIT candidate, is an Fc-silent investigational monoclonal antibody that binds to TIGIT, a protein receptor on immune cells that acts as a brake on the immune response. Cancer cells can exploit TIGIT to avoid detection by the immune system. Domvanalimab binds to TIGIT to free up immune activating pathways and activate immune cells to attack and kill cancer cells.

Treatment with domvanalimab, an Fc-silent antibody, has not been associated with the depletion of peripheral regulatory T-cells. We believe this may result in fewer infusion reactions relative to what has been reported for other anti-TIGIT-containing regimens.

Arcus is developing a second anti-TIGIT candidate, AB308, an Fc-enabled investigational monoclonal antibody. AB308 is currently in a Phase I study for advanced malignancies.

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 in to all other Arcus programs arising during the collaboration term. For clinical programs in existence at the date of the agreement, Gilead’s opt-in payment ranges from $200 million to $275 million per program. For all other 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 prescribed 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 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 19.5%, with an additional $220 million investment.

On November 8, 2021 Day One Biopharmaceuticals (Nasdaq: DAWN), a clinical-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for patients of all ages with genomically defined cancers, reported financial results for the third quarter of 2021 and highlighted recent corporate achievements (Press release, Day One, NOV 8, 2021, View Source [SID1234594718]).

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"We continue to build momentum in our lead program with the granting of Rare Pediatric Disease Designation for DAY101 for the treatment of pediatric low-grade glioma during the third quarter," said Jeremy Bender, Ph.D., chief executive officer of Day One. "Additionally, with the further strengthening of our leadership team and continued progress with enrollment in our pivotal Phase 2 study, FIREFLY-1, we remain on track to present initial clinical data from this trial in the first half of 2022. We continue to grow our company, advance our development programs, and work to achieve our mission of impacting the lives of all people with cancer, whatever their age, starting from Day One."

Program Highlights

FIREFLY-1, a pivotal Phase 2 clinical trial of DAY101 in pediatric low-grade glioma (pLGG), continues active enrollment; initial data are expected in the first half of 2022. The single arm, open-label, global registrational Phase 2 study is anticipated to enroll 60 patients and has activated approximately 25 sites globally.

Day One will present a poster at the 2021 Connective Tissue Oncology Society (CTOS) Virtual Annual Meeting on November 12, 2021. The poster reviews a compassionate use case of a child with recurrent spindle cell sarcoma harboring a novel SNX8-BRAF gene fusion who had exhausted all treatment options, including a MEK inhibitor, and was treated with DAY101 monotherapy. Following treatment, the patient’s symptoms resolved and there was no evidence of measurable disease at the site of previously visualized tumor, indicating a complete response to treatment with DAY101.

Day One is also conducting a Phase 2 monotherapy trial of DAY101 in adult patients with recurrent, progressive, or refractory solid tumors harboring MAPK pathway aberrations.
Corporate Highlights

Day One strengthened its leadership team with appointment of Jaa Roberson as chief people officer. Ms. Roberson will oversee all aspects of Day One’s human resources and talent acquisition efforts as the Company continues to grow.

The Company recently expanded its board of directors with the appointment of Scott Garland. Mr. Garland is a 30-year veteran of the biopharmaceutical industry with deep commercial and executive leadership experience.
Third Quarter 2021 Financial Highlights

Cash Position: Cash and cash equivalents and short-term investments totaled $297.2 million at September 30, 2021. Based on Day One’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations into the second half of 2023.

R&D Expenses: Research and development expenses were $9.8 million for the third quarter 2021 compared to $2.5 million for the third quarter 2020. The increase was primarily due to additional employee compensation costs, clinical trial expenses, and CMC activity.

G&A Expenses: General and administrative expenses were $9.4 million for the third quarter 2021 compared to $1.0 million for the third quarter 2020. The increase was primarily due to additional employee compensation costs, legal, and professional expenses associated with operating as a public company.

Net Loss: Net loss totaled $19.2 million and $3.8 million for the third quarters of 2021 and 2020, respectively, with non-cash stock compensation expense of $5.1 million and $0.1 million for the third quarters of 2021 and 2020, respectively.
Upcoming Events

Connective Tissue Oncology Society (CTOS) Virtual 2021 Annual Meeting (November 10-13, 2021) Day One will present the following poster:

Title: "Activity of Pan-Raf Inhibitor Day101 in a Pediatric Patient with a Recurrent Spindle Cell Sarcoma Harboring a Novel SNX8:BRAF Gene Fusion"
Presenter: Katherine Offer, MD
Date: Friday, November 12, 2021
Time: 2:30 PM – 3:15 PM EST
30th Annual Credit Suisse Virtual Healthcare Conference, November 8-11, 2021
33rd Annual Piper Sandler Healthcare Conference, November 29-December 3, 2021
About DAY101
DAY101 is an investigational, oral, brain-penetrant, highly-selective type II pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway. Studies have shown DAY101 has high brain distribution and exposure in comparison to other MAPK pathway inhibitors, thus potentially benefiting patients with primary brain tumors or brain metastases of solid tumors. DAY101 is a type II RAF inhibitor found to selectively inhibit both monomeric and dimeric RAF kinase, which may broaden its potential clinical application to treat an array of RAF-altered tumors.

DAY101 has been studied in over 250 patients, and as a monotherapy demonstrated good tolerability and encouraging anti-tumor activity in pediatric and adult populations with specific MAPK pathway-alterations. In November 2020, Day One announced preliminary results from PNOC014, an ongoing Phase 1 Pacific Pediatric Neuro-Oncology Consortium (PNOC) network study with DAY101 sponsored by the Dana-Farber Cancer Institute. Preliminary results demonstrated that of the eight relapsed pLGG patients in the study with RAF fusions, two patients achieved a complete response by Response Assessment for Neuro-Oncology (RANO), three had a partial response, two achieved prolonged stable disease, and one experienced progressive disease. DAY101 also demonstrated a tolerable safety profile with the most common side effects being skin rash and hair color changes.

DAY101 has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pLGG harboring an activating RAF alteration who require systemic therapy and who have either progressed following prior treatment or who have no satisfactory alternative treatment options. The FDA has also granted Rare Pediatric Disease Designation to DAY101 for the treatment of low-grade gliomas harboring an activating RAF alteration that disproportionately affects children. In addition, DAY101 has received Orphan Drug designation from the FDA for the treatment of malignant glioma and orphan designation from the European Commission for the treatment of glioma.

Day One is conducting a pivotal Phase 2 trial (FIREFLY-1) of DAY101 in pediatric, adolescent and young adult patients with pLGG. Day One also plans to study DAY101 alone or in combination with other agents that target key signaling nodes in the MAPK pathway, such as the Company’s MEK inhibitor pimasertib, in patient populations where various RAS and RAF alterations are believed to play an important role in driving disease.

On November 8, 2021 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics (RCT) for the treatment of cancer and autoimmune diseases, reported third quarter 2021 financial results and provided a business update (Press release, Rubius Therapeutics, NOV 8, 2021, View Source [SID1234594734]).

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"With the clearance of our latest IND application for RTX-224, we will have three Red Cell Therapeutic product candidates for the potential treatment of cancer in the clinic, demonstrating continued strong execution across preclinical and clinical development as well as manufacturing," said Larry Turka, M.D., chief scientific officer and head of research and translational medicine. "As shown in our preclinical studies, RTX-224 is designed to activate CD8+ and CD4+ T cells, promote antigen presentation and activate and expand NK cells to produce a broad and potent anti-tumor T cell response in solid tumor cancers with known sensitivity to T cell killing, including tumor types with high mutational burden, PD-L1 expression and prior responsiveness to checkpoint inhibitors."

Dr. Turka has been promoted to chief scientific officer and head of research & translational medicine. Joining Rubius Therapeutics as chief scientific officer in January 2020, Larry is an internationally recognized physician-scientist in autoimmunity and translational immunology with a distinguished career working in academia and, more recently, in the biotechnology industry where he has built a portfolio of novel therapies targeting immune cells.

"Larry’s impressive record of scientific achievement in immunology and ability to foster an environment of innovation has been instrumental in integrating our preclinical and clinical development programs. As Rubius enters a period of potentially significant clinical data generation, we look forward to leveraging Larry’s expertise in translational medicine and building our clinical development strategy," said Pablo J. Cagnoni, M.D., president and chief executive officer.

Along with this leadership change, chief medical officer Christina Coughlin, M.D., Ph.D., will be leaving Rubius Therapeutics to pursue another opportunity as chief executive officer, and she will continue to serve as an advisor to the Company during a transition period following her resignation. The Company thanks her for her contributions to Rubius and wishes her the best in the next chapter of her career.

Third Quarter 2021 and Recent Highlights

Clinical Development in Oncology

Enrollment continues across Rubius’ portfolio of Red Cell Therapeutics for the treatment of cancer:
The Phase 1 arms of single-agent RTX-240 in advanced solid tumors and relapsed/refractory AML.
The Company plans to present comprehensive results by the end of 2021 or during the first quarter of 2022.
The Phase 1 arm of the ongoing Phase 1/2 RTX-240 clinical trial in combination with KEYTRUDA (pembrolizumab) for advanced solid tumors.
To be eligible for the trial, patients must have disease that is relapsed or refractory to an anti-PD-1 or PD-L1 therapy. With its mechanism of action as a broad immune agonist, RTX-240 may have synergy with immune checkpoint inhibition and potentially overcome resistance to PD-1 inhibition.
The Phase 1 clinical trial of RTX-321 in patients with advanced HPV 16-positive cancers, including cervical, head & neck cancers, and anal cancer.
The company plans to present initial clinical results during the first quarter of 2022.
U.S. FDA cleared the IND application for RTX-224, Rubius’ third oncology product candidate.
The company expects to dose its first patient during the first quarter of 2022.
Peer-Reviewed Publications and Poster Presentations at Medical Conferences

The Company plans to present preclinical data for RTX-224 at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting on November 12th at 8:00 a.m. ET.
The data indicates that RTX-224 activates immune cells in the spleen and blood, leading to their trafficking into the tumor microenvironment to deliver an antitumor effect in preclinical models.
In July 2021, the manuscript entitled "Anti-Tumor Effects of RTX-240: an Engineered Red Blood Cell Expressing 4-1BB Ligand and Interleukin-15" was published in the peer-reviewed journal Cancer Immunology, Immunotherapy, highlighting preclinical findings for RTX-240, which demonstrated that RTX-240 activates and expands CD8+ T cells and NK cells in vitro and in vivo generating potent anti-tumor activity in both a colorectal and melanoma model.
Near-Term Catalysts and Operational Objectives

Present additional clinical data from the RTX-240 solid tumor Phase 1 clinical trial at the end of 2021 or during the first quarter of 2022;
Select specific solid tumor types that will be pursued in the Phase 2 expansion cohorts of RTX-240;
Report initial clinical data from the Phase 1 arm of the RTX-240 clinical trial in relapsed/refractory AML at the end of 2021 or during the first quarter of 2022; and
Report initial Phase 1 clinical data from RTX-321 for the treatment of HPV 16-positive cancers by the first quarter of 2022.
Initiate Phase 1 clinical trial for RTX-224 in advanced solid tumors during the first quarter of 2022.
Third Quarter Financial Results

Net loss for the third quarter of 2021 was $49.0 million or $0.55 per common share, compared to $40.9 million or $0.51 per common share in the third quarter of 2020.

In the third quarter of 2021, Rubius invested $38.0 million in research and development (R&D) related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $28.2 million in the third quarter of 2020. This year-over-year increase was principally due to a $6.8 million increase in costs incurred for the Company’s lead cancer programs, RTX-240 and RTX-321, primarily from clinical research organization (CRO) and internal manufacturing costs incurred in connection with the three Phase 1 arms of its Phase 1/2 clinical trial of RTX-240 and for its Phase 1 clinical trial of RTX-321 for the treatment of HPV16-positive cancers. Additionally, personnel-related costs increased $1.6 million principally for additions to headcount to support the Company’s expanded operations and stock-based compensation increased by $1.4 million.

General and administrative (G&A) expenses were flat at $12.0 million during the third quarter of 2021, as compared to the third quarter of 2020. While there were increases totaling $1.3 million across professional fees, facility and personnel costs, they were offset by a decline in stock-based compensation expense of $1.2 million following the full vesting of large awards early in the third quarter of 2021.

Nine Month Financial Results

Net loss for the first nine months of 2021 was $141.5 million or $1.62 per common share, compared to $127.2 million or $1.58 per common share in the first nine months of 2020.

In the nine months ended September 30, 2021, Rubius invested $101.8 million in R&D related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $90.5 million in the first nine months of 2020. The year-over-year increase was driven primarily by a $17.7 million increase in costs for the Company’s lead cancer programs, including CRO and internal manufacturing costs. These costs were associated with the three arms of its Phase 1/2 clinical trial of RTX-240 as well as costs incurred for its Phase 1 clinical trial of RTX-321 in patients with advanced HPV 16-positive cancers. This increase was partially offset by a $7.0 million reduction in rare disease program costs, following the deprioritization of the Company’s rare disease pipeline in March 2020. Additionally, platform development, early-stage research and other unallocated expenses increased by $0.6 million. This consisted of $2.8 million in additional stock-based compensation and a $1.7 million increase in personnel and facility related costs, which were partially offset by reductions in contract R&D, laboratory supplies and research materials as research activities shifted to support clinical programs.

G&A expenses were $39.1 million during the first nine months of 2021, as compared to $36.2 million for the same period in 2020. The higher costs were driven by a $2.4 million increase in personnel and facility related costs, as well as a $1.6 million increase in professional and consultant fees. These increases were offset by a decrease in stock-based compensation expense of $1.1 million, following the vesting of large awards early in the third quarter of 2021.

Cash Position

As of September 30, 2021, cash and cash equivalents were $264.0 million, compared to $176.3 million in cash, cash equivalents and investments as of December 31, 2020. In connection with its underwritten public offering completed in March 2021, the Company received net proceeds of $187.2 million, after deducting underwriting discounts and commission and other offering costs. In addition, in June 2021, the Company amended its debt facility, postponing principal payments by two and a half years, until mid-2024.

About Red Cell Therapeutics
Red Cell Therapeutics (RCTs) are a new class of allogeneic, off-the-shelf cellular therapeutic candidates for the treatment of cancer and autoimmune diseases. For the treatment of cancer, RCTs are expected to provide advantages over other therapies by potentially generating a broad anti-tumor response with limited side effects and a wide therapeutic window given the biodistribution of RCTs to the vasculature and spleen. Additionally, RCTs do not have the complex supply chain and administration logistics of other cell therapies, as RCTs are designed to be prepared in the pharmacy, administered in an outpatient setting and do not require lymphodepletion prior to administration.

About RTX-240
RTX-240, Rubius Therapeutics’ lead oncology program, is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand (4-1BBL) and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms. RTX-240 is designed to broadly stimulate the immune system by activating and expanding both NK and memory T cells to generate a potent anti-tumor response.

About RTX-321
RTX-321, the Company’s second oncology program, is an allogeneic, off-the-shelf aAPC therapy product candidate that is engineered to induce a tumor-specific immune response by expanding antigen-specific T cells. RTX-321 expresses hundreds of thousands of copies of an HPV peptide antigen bound to major histocompatibility complex class I proteins, the costimulatory molecule 4-1BBL and the cytokine IL-12 on the cell surface to mimic human T cell-APC interactions.

About RTX-224
RTX-224 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to express hundreds of thousands of copies of 4-1BBL and IL-12 on the cell surface. In contrast to RTX-240, RTX-224 is designed as a broad immune agonist of both adaptive and innate responses, activating CD8+ and CD4+ T cells, promoting antigen presentation and activating and expanding NK cells. It is expected to produce a broad and potent anti-tumor T cell response, an innate immune response and have anti-tumor activity in those tumor types with known sensitivity to T cell killing, including tumor types with high mutational burden, PD-L1 expression and prior activity of checkpoint inhibitors.

On November 8, 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 financial results for the third quarter ended September 30, 2021 and provided a review of recent business and portfolio highlights, including initial data from the Phase 1 study of XmAb306, an IL15-Fc cytokine, in patients with advanced solid tumors (Press release, Xencor, NOV 8, 2021, View Source [SID1234594751]).

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"This year we have significantly advanced our portfolio of clinical-stage XmAb drug candidates, establishing Phase 2 development plans for vudalimab, plamotamab and tidutamab. In the coming weeks, we will present new clinical data from the Phase 1 studies of vudalimab at SITC (Free SITC Whitepaper) and plamotamab at ASH (Free ASH Whitepaper)," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Looking ahead to next year, we are on track to initiate first-in-human studies for additional XmAb drug candidates, such as XmAb819, our first 2+1 bispecific antibody, which targets the underexplored kidney tumor target ENPP3, and XmAb808, our first tumor-selective, co-stimulatory CD28 bispecific antibody, which targets the broadly expressed tumor antigen B7-H3.

"Today we have announced encouraging initial dose-escalation data from our first clinical-stage cytokine, XmAb306, which is co-developed in collaboration with Genentech, a member of the Roche Group. Exceptional NK cell expansion of 40- to 100-fold increases compared to baseline, with good tolerability to date, has been observed. As we continue to escalate, we are now observing signs of effector T cell proliferation in the periphery. XmAb306’s safety profile, biological activity and preliminary signs of anti-tumor activity at this early stage provide initial validation for our reduced-potency approach to engineering XmAb cytokine therapeutics, and we are considering new trials to study combinations with a range of NK and T-cell recruiting therapies."

Portfolio Highlights and Upcoming Data Presentations

Plamotamab (CD20 x CD3): Xencor entered a collaboration with Janssen to advance plamotamab and XmAb CD28 bispecific antibody combinations for the treatment of patients with B-cell malignancies, which expands the Company’s strategy to develop multiple highly active, chemotherapy-free regimens to treat patients with B-cell cancers. Janssen received worldwide exclusive development and commercial rights to plamotamab, and the Company will collaborate with Janssen on further clinical development of plamotamab, with Xencor paying 20% of costs, including those for a subcutaneous formulation study anticipated to enter clinical trials in 2022. The Company will continue, at its own expense, the combination study of plamotamab, tafasitamab and lenalidomide.

The Company will present updated clinical results from the Phase 1 study of plamotamab in patients with non-Hodgkin lymphoma during the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2021.
Vudalimab (PD-1 x CTLA-4): The Company will announce updated clinical results from expansion cohorts in the Phase 1 study in patients with prostate cancer, renal cell carcinoma and in cancers without approved checkpoint therapies during the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) on November 12. A Phase 2 study in patients with metastatic castration-resistant prostate cancer, evaluating vudalimab as a monotherapy or in combination with other agents depending on the tumor’s molecular subtype, is now enrolling patients.
Tidutamab (SSTR2 x CD3): Updated clinical data from a Phase 1 study in patients with neuroendocrine tumors (NETs) were presented during the North American Neuroendocrine Tumor Society’s 2021 Multidisciplinary NET Medical Virtual Symposium (NANETS). A Phase 1b/2 clinical study in patients with Merkel cell carcinoma and small cell lung cancer, which are SSTR2-expressing tumor types known to be responsive to immunotherapy, is now enrolling patients.
Vibecotamab (CD123 x CD3): The Company was notified that Novartis is terminating its rights with respect to the vibecotamab program, which will be effective February 2022. The Company does not intend any further internal development of vibecotamab.
Preclinical Data Presentations: New data from four preclinical-stage programs, including Xencor’s IL-12-Fc cytokine program, PD-L1 x CD28 bispecific antibody program, TGFβR2 bispecific antibody platform, and bispecific NK cell engager platform, will also be presented at the SITC (Free SITC Whitepaper) Annual Meeting.
XmAb306 Promotes High Levels of Sustained NK Cell Expansion in Ongoing Phase 1 Dose-Escalation Study

XmAb306 is a potency-reduced IL15/IL15Rα-Fc fusion protein that incorporates Xtend extended half-life technology, and Xencor is co-developing the program in collaboration with Genentech, a member of the Roche Group. An ongoing Phase 1 dose-escalation study of XmAb306 in patients with advanced solid tumors has enrolled six cohorts in a monotherapy arm and four cohorts in an atezolizumab combination arm, and further dose escalation in both study arms is continuing.

XmAb306 has been generally well tolerated as both a monotherapy and in combination with atezolizumab. No dose-limiting toxicities or treatment-related serious adverse events have been observed to date. Assessments of pharmacokinetics indicate that XmAb306 has a multi-day circulating half-life, which is consistent with its reduced-potency design and data generated in preclinical studies. Unconfirmed responses, as evaluated by RECIST criteria, have been observed in multiple tumor types, including in a patient treated with XmAb306 monotherapy.

In recently dosed cohorts, the study has reached dose levels that promote T cell activity, and evidence of peripheral effector T cell proliferation has been observed. Consistent and robust dose-dependent natural killer (NK) cell expansion and NK cell accumulation upon repeat dosing has been observed for multiple NK cell subsets, including mature NK cells. Significant NK cell expansion and accumulation was observed beginning in lower dose cohorts, and at higher dosing cohorts NK cell expansion has reached 40- to 100-fold higher levels than baseline and has been sustained for weeks throughout dosing.

Additional studies of XmAb306 in combination with other agents are being planned. Under its agreement with Genentech, Xencor shares in 45 percent of worldwide development and commercialization costs for XmAb306 and will receive a share of net profits or net losses from product sales at the same percentage rate.

Xencor’s potency-reduced, engineered cytokines are designed to expand select immune cell populations, to have longer circulating half-life and to be tolerable, active and easy to administer. In addition to developing XmAb306, Xencor is conducting a Phase 1 study of XmAb564, a regulatory T cell-biased IL2-Fc cytokine for autoimmune disease, in healthy volunteers. The Company plans to submit an IND application for XmAb662, an IL12-Fc cytokine in 2022.

Other Partnership Updates

MorphoSys AG: In August 2021, the European Commission granted conditional marketing authorization for Minjuvi (tafasitamab) in combination with lenalidomide, followed by tafasitamab monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma who are not eligible for autologous stem cell transplantation. Tafasitamab was created and initially developed by Xencor and is co-marketed by Incyte and MorphoSys under the brand name Monjuvi in the U.S. and is marketed by Incyte under the brand name Minjuvi in the E.U. Monjuvi and Minjuvi are registered trademarks of MorphoSys AG.
Vir Biotechnology, Inc.: Vir and its partner GlaxoSmithKline (GSK) have made progress increasing global patient access to sotrovimab, an investigational SARS-CoV-2 monoclonal antibody for the treatment of mild-to-moderate COVID-19 in high-risk adults and pediatric patients. Sotrovimab has received emergency use authorization in the U.S., a positive scientific opinion from the Committee for Human Medicinal Products in the European Union, and emergency or temporary use authorizations in many other countries. Sotrovimab incorporates Xencor’s Xtend Fc technology for longer duration of action.
Third Quarter Ended September 30, 2021 Financial Results

Cash, cash equivalents, receivables and marketable debt securities totaled $537.9 million at September 30, 2021, compared to $610.2 million at December 31, 2020. The decrease reflects cash used to fund operating activities in the first nine months of 2021, offset by proceeds from royalties, milestone payments and the sale of an investment security. The September 30, 2021 balance excludes payments due to Xencor under the Janssen Collaboration which include a $100 million upfront payment and a $25 million payment for the sale of Xencor common stock which the Company expects to receive before year-end.

Total revenue for the third quarter ended September 30, 2021 was $19.7 million, compared to $35.4 million for the same period in 2020. Revenues in the third quarter were primarily related to revenue earned under the Company’s first Janssen collaboration and royalty revenue, compared to revenues from the same period in 2020, which was primarily a milestone payment from MorphoSys. Total revenue for the nine months ended September 30, 2021 was $121.1 million, compared to $80.8 million for the same period in 2020. Revenues for the nine-month period in 2021 were primarily earned from research collaborations with Janssen, Genentech and Novartis, milestone revenue from MorphoSys and Novartis, and royalty revenue, compared to the same period in 2020, which were primarily milestone revenue from MorphoSys and licensing revenue from Gilead, Aimmune and Omeros.

Research and development (R&D) expenses for the third quarter ended September 30, 2021 were $50.6 million, compared to $44.5 million for the same period in 2020. Total R&D expenses for the nine months ended September 30, 2021 were $141.5 million, compared to $121.9 million for the same period in 2020. Increased R&D expenses for the third quarter and first nine months of 2021 over amounts for the same periods in 2020 were primarily due to additional spending on IL-15 drug candidate programs and other early-stage programs. Additional spending on XmAb819 also contributed to increased R&D expenses during the third quarter of 2021.

General and administrative (G&A) expenses for the third quarter ended September 30, 2021 were $10.4 million, compared to $7.6 million for the same period in 2020. Total G&A expenses for the nine months ended September 30, 2021 were $27.5 million, compared to $22.1 million for the same period in 2020. Increased G&A expenses for the third quarter and first nine months of 2021 over amounts for the same periods in 2020 were primarily due to increased G&A staffing and spending on professional services and facility costs.

Total other income, net, for the third quarter ended September 30, 2021 was $1.1 million, compared to $4.2 million in the same period in 2020. Other income for the nine months ended September 30, 2021 was $57.5 million, compared to $7.5 million in the same period in 2020. Other income for the first nine months of 2021 includes realized gains on the sale of an investment equity security and an increase in unrealized gains on the Company’s marketable equity investments.

Non-cash, stock-based compensation expense for the nine months ended September 30, 2021 was $26.6 million, compared to $23.1 million for the same period in 2020.

Net loss for the third quarter ended September 30, 2021 was $40.2 million, or $(0.69) on a fully diluted per share basis, compared to net loss of $12.6 million, or $(0.22) on a fully diluted per share basis, for the same period in 2020. The increased net loss reported for the third quarter, compared to the same period of 2020, was primarily due to lower milestone revenue and higher operating expenses in 2021. For the nine months ended September 30, 2021, net income was $9.6 million, or $0.16 on a fully diluted per share basis, compared to net loss of $55.6 million, or $(0.97) on a fully diluted per share basis, for the same period in 2020. Net income reported for the first nine months of 2021, compared to the net loss reported for the same period in 2020, was primarily due to higher collaboration revenues and realized and unrealized gains from equity investment securities in 2021 compared to 2020.

The total shares outstanding were 58,454,811 as of September 30, 2021, compared to 57,374,937 as of September 30, 2020.

Financial Guidance

Based on current operating plans, Xencor expects to have cash to fund research and development programs and operations into 2025. Xencor expects to end 2021 with between $575 million and $625 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 these third quarter 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 5536153. A live webcast of the conference call will be available online from the Investors section of Xencor’s website at www.xencor.com. The webcast will be archived on Xencor’s website for 30 days.