On November 9, 2020 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, reported third quarter 2020 financial results and provided an overview of operational progress (Press release, Rubius Therapeutics, NOV 9, 2020, View Source [SID1234570326]).

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"Rubius Therapeutics continues to demonstrate strong execution across our pipeline of Red Cell Therapeutics for the treatment of cancer. Our IND filing for RTX-321 included, for the first time, frozen drug substance as part of the manufacturing process, resulting in a truly off-the-shelf cellular therapy with a potential shelf life of up to several years," said Pablo J. Cagnoni, M.D., president and chief executive officer of Rubius Therapeutics. "As we continue to escalate the dose in the RTX-240 solid tumor trial, we are assessing the safety profile and biological effects of RTX-240 on innate and adaptive immune responses. We believe that by demonstrating that RTX-240 is working as intended to induce anti-tumor innate and adaptive immunity, we can unlock the potential of the RED PLATFORM across our entire pipeline of cancer and autoimmune programs."

Third Quarter and Recent Highlights

RTX-240 Phase 1/2 Clinical Program for Advanced Solid Tumors or Relapsed/Refractory Acute Myeloid Leukemia (AML)

Completed dosing of the fourth cohort in the Phase 1/2 solid tumor clinical trial
Assessing the safety profile and biological effects of RTX-240 on innate and adaptive immune responses by measuring biomarkers associated with activation and proliferation of NK and T cells in both peripheral blood and paired tumor biopsy samples across dose levels
Dosed the first patient with relapsed or refractory AML in second Phase 1 arm of ongoing RTX-240 clinical trial
Demonstrating robust momentum in manufacturing and producing clinical supply of RTX-240 for both arms in the Phase 1/2 clinical trial of RTX-240
RTX-321 Artificial Antigen-Presenting Cell (aAPC) Development Program for Human Papillomavirus (HPV) 16-Positive Cancers

Filed an IND with U.S. FDA for RTX-321 for the treatment of HPV 16-positive cancers
For the first time, the IND filing includes frozen drug substance as part of the manufacturing process, resulting in a truly off-the-shelf cellular therapy with a potential shelf life of up to several years
Conducting manufacturing in support of planned GMP clinical supply needs for the RTX-321 clinical trial
Leadership Team

Strengthened the leadership team by appointing Jose "Pepe" Carmona as chief financial officer
Pepe brings to Rubius extensive experience in global finance and operations, as well as a track record of financing clinical-stage and commercial biotech companies
Preclinical Data Presentations

This morning, Rubius presented preclinical data from its lead clinical oncology candidate, RTX-240, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting, demonstrating:
RTX-240 increased CD8 T cell and NK cell expansion and activation in vitro when compared to a combination of 4-1BB agonist antibody plus recombinant IL-15, which was directly correlated with the percentage of 4-1BBL and IL-15TP expressed on the cell surface
RTX-240 expanded CD56dim NK cells, a cell population with high cytotoxicity
RTX-240 promoted NK cell-killing of a myeloid leukemia cell line, K562, which was accompanied by increased NK cell degranulation and activation
A murine surrogate for RTX-240, mRBC-240, promoted significant expansion of CD8 T cells and NK cells in vivo in a murine model of colorectal cancer (CT26)
mRBC-240 demonstrated potent antitumor activity in a B16F10 melanoma model that was directly correlated with the expansion of terminally differentiated NK cells in the tumors
Presented preclinical data at the Federation of Clinical Immunology Societies Annual Meeting and the American Association of Cancer Research Tumor Immunology and Immunotherapy Conference, from its lead aAPC program, RTX-321, for the treatment of HPV 16-positive tumors demonstrating:
RTX-321 and its mouse surrogates demonstrated a dual mechanism of action in vivo
Functions as an aAPC to boost antigen-specific CD8+ T cell responses
Promotes antigenindependent stimulation of both innate and adaptive immune responses
Mouse surrogates of RTX-321 promote tumor control, memory formation and epitope spreading in tumor models in vivo
Treatment with the RTX-321 mouse surrogate results in minimal, reversible effects in vivo, likely due to biodistribution to the vasculature and spleen
RTX-321 functions as an aAPC to boost HPV 16 antigen-specific T cells in vitro
RTX-321 promotes HPV 16-independent adaptive and innate immune responses in vitro
Third Quarter Financial Results

Net loss for the third quarter of 2020 was $40.9 million or $0.51 per common share, compared to $47.0 million or $0.59 per common share in the third quarter of 2019.

In the third quarter of 2020, Rubius invested $28.2 million in research and development (R&D) related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $33.5 million in the third quarter of 2019. The year-over-year decrease was driven by a $7.5 million reduction in costs following the deprioritization of our rare disease pipeline in March 2020. The decrease in rare disease program expenses was offset by $9.6 million in incremental spend to advance our cancer programs, including costs associated with our Phase 1/2 clinical trial for RTX-240 for the treatment of solid tumors as well as costs associated with preclinical and IND-enabling activities for RTX-321. In addition, R&D expenses not allocated to programs decreased by $7.4 million driven primarily by reductions in non-program labor, laboratory supplies, research materials and contract research as pre-GMP manufacturing and discovery activities shifted to support the development of clinical candidates.

G&A expenses were $12.0 million during the third quarter of 2020, as compared to $15.0 million for the third quarter of 2019. The lower costs were principally driven by a reduction in stock-based compensation expense.

Nine Month Financial Results

Net loss for the first nine months of 2020 was $127.2 million or $1.58 per common share, compared to $119.0 million or $1.52 per common share in the first nine months of 2019.

In the nine months ended September 30, 2020, Rubius invested $90.5 million in R&D related to its novel RED PLATFORM and towards expanding and advancing its product pipeline, as compared to $81.9 million in the first nine months of 2019. The year-over-year increase was driven by $28.3 million of incremental costs to advance our cancer programs, including costs incurred for our Phase 1/2 clinical trial for RTX-240 for the treatment of solid tumors as well as costs of preclinical and IND-enabling activities for RTX-321. The increase in cancer program costs was offset by a $12.8 million decrease in expenses related to our rare disease pipeline following the deprioritization of these programs in March 2020. Additionally, costs not allocated to programs decreased by $6.9 million driven primarily by a shift in manufacturing activities towards the technical development and production of clinical supply for our oncology programs and the shift in discovery activities from the development of clinical candidates towards work to support IND enabling activities.

G&A expenses were $36.2 million during the first nine months of 2020, as compared to $42.3 million for the same period in 2019. The lower costs were principally driven by a reduction in stock-based compensation expense.

Cash Position

As of September 30, 2020, cash, cash equivalents and investments were $207.9 million as compared to $283.3 million as of December 31, 2019, providing Rubius with a cash runway into 2022. During 2020, the Company used $97.1 million of cash to fund operations and $4.5 million to fund capital expenditures, consisting mostly of payments for assets purchased in 2019. In addition, during 2020 the Company drew down the third and final tranche of $25.0 million pursuant to its $75.0 million loan agreement with Solar Capital.

On November 9, 2020 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported third quarter and year-to-date financial results for 2020 (Press release, Precigen, NOV 9, 2020, View Source [SID1234570325]).

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Business Highlights:

Clinical Pipeline and Data Update Conference Call: In light of the substantive progress made in advancing its clinical pipeline, as well as anticipated data disclosures for several key programs, Precigen will host a conference call in early December dedicated to reviewing these important milestones. The Company plans to announce timing and details about the call in the coming weeks;
UltraPorator: Precigen announced that the US Food and Drug Administration (FDA) cleared UltraPorator as a manufacturing device for its UltraCAR-T manufacturing process. The Company announced that it has successfully completed technology transfer of the UltraPorator system for the manufacturing of PRGN-3005 in ovarian cancer at the University of Washington/Fred Hutchinson Cancer Research Center and for PRGN-3006 in acute myeloid leukemia (AML) at the Moffitt Cancer Center. UltraPorator is a semi-closed, high-throughput system with a proprietary hardware and software solution designed to significantly reduce processing time and contamination risk, limitations inherent in existing electroporation devices that contribute to current hurdles for viable scale-up and commercialization of certain therapeutic programs;
PRGN-2009 AdenoVerse Immunotherapy: Precigen announced that the first patient has been dosed in the Phase I/II trial for PRGN-2009, a first-in-class, off-the-shelf investigational immunotherapy utilizing the AdenoVerse platform and designed to activate the immune system to recognize and target HPV-positive solid tumors;
PRGN-3005 UltraCAR-T: Precigen completed dosing of patients in dose level 3 of the intraperitoneal (IP) arm of the Phase 1 clinical trial of PRGN-3005 UltraCAR-T for the treatment of advanced, recurrent platinum resistant ovarian, fallopian tube or primary peritoneal cancer (clinical trial identifier: NCT03907527); and
PRGN-3006 UltraCAR-T: Precigen completed dosing of patients in dose level 2 of the non-lymphodepletion arm and dose level 1 in the lymphodepletion arm of the Phase 1 trial of PRGN-3006 UltraCAR-T for treatment of patients with relapsed or refractory acute myeloid leukemia (AML) or higher-risk myelodysplastic syndromes (MDS) (clinical trial identifier: NCT03927261).
"The Precigen team has made impressive progress this quarter in driving value across our preclinical and clinical pipeline. In particular, we made several advances in our quest to meet unmet needs for patients, including dosing the first patient in our first-in-human study of PRGN-2009 AdenoVerse in HPV-positive solid tumors, and advancing our proprietary UltraPorator system towards clinical implementation," said Helen Sabzevari, PhD, President and CEO of Precigen. "In early December, we are excited to share a comprehensive update on our clinical pipeline progress towards meeting our 2020 goals laid out earlier this year as well as looking forward to the PRGN-3006 presentation at the 2020 meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) by the trial’s Principal Investigator, Dr. David Sallman from the Moffitt Cancer Center."

Third Quarter 2020 Financial Highlights:

Total revenues of $23.6 million in 2020 compared to $18.3 million in 2019;
Net loss from continuing operations of $29.5 million, or $(0.18) per basic share, of which $10.1 million was for non-cash charges in 2020, compared to net loss from continuing operations of $49.1 million, or $(0.32) per basic share, of which $15.7 million was for non-cash charges in 2019; and
Cash, cash equivalents, and short-term investments totaled $113.1 million as of September 30, 2020.
Year-to-Date 2020 Financial Highlights:

Total revenues of $83.8 million in 2020 compared to $73.7 million in 2019; and
Net loss from continuing operations of $102.8 million, or $(0.63) per basic share, of which $50.6 million was for non-cash charges in 2020 compared to net loss from continuing operations attributable to Precigen of $132.7 million, or $(0.86) per basic share, of which $36.2 million was for non-cash charges in 2019.
Third Quarter 2020 Financial Results Compared to Prior Year Period

Total revenues increased $5.3 million, or 29%, over the quarter ended September 30, 2019. Collaboration and licensing revenues increased $2.9 million primarily due to the accelerated recognition of previously deferred revenue upon the mutual termination of one of the Company’s collaboration agreements in July 2020. Product and service revenues generated by the Company’s Trans Ova and Exemplar subsidiaries increased $2.4 million due to an increase in services performed for new and existing customers and the expansion of Trans Ova’s commercial dairy business. Gross margin on products and services improved as a result of operational efficiencies gained through reductions in workforce and improved inventory management as well as a decrease in the cost of cows used in production.

Research and development expenses decreased $13.5 million, or 53%, from the quarter ended September 30, 2019. Salaries, benefits, and other personnel costs decreased $6.8 million and contract research organization costs and lab supplies decreased $5.1 million as Precigen suspended the operations of its MBP Titan subsidiary in the second quarter and deprioritized certain internal programs at its ActoBio subsidiary in the fourth quarter of 2019. Selling, general and administrative (SG&A) expenses were comparable period over period.

Year-to-Date 2020 Financial Results Compared to Prior Year Period

Total revenues increased $10.1 million, or 14%, over the nine months ended September 30, 2019 primarily due to an increase in Precigen’s collaboration and licensing revenues as the Company accelerated the recognition of previously deferred revenue upon the mutual termination of two of its collaboration agreements in 2020. Product and service revenues generated by Trans Ova and Exemplar increased $4.8 million due to an increase in services performed for new and existing customers and the expansion of Trans Ova’s commercial dairy business. Gross margin on products and services improved as a result of operational efficiencies gained through reductions in workforce, improved inventory management, a reduction in third-party royalty rate obligations for certain licensed technologies and a decrease in the cost of cows used in production.

Research and development expenses decreased $35.6 million, or 44%, from the nine months ended September 30, 2019. Salaries, benefits, and other personnel costs decreased $13.7 million and contract research organization costs and lab supplies decreased $17.9 million as Precigen suspended the operations of its MBP Titan subsidiary in the second quarter and deprioritized certain internal programs at its ActoBio subsidiary in the fourth quarter of 2019. SG&A expenses decreased $8.4 million and include a net decrease in fees payable to certain third-party vendors and a reduction of 30% in corporate headcount to support a more streamlined organization. Other corporate expenses decreased $1.9 million as part of the streamlined organization and the impact of the COVID-19 pandemic on travel. These decreases were partially offset by increased share-based compensation expense attributable to equity grants made in in the first quarter of 2020 and one-time severance costs for terminated employees. The Company also recorded $23.0 million of impairment charges for the nine months ended September 30, 2020 primarily due to the write down of goodwill and intangible assets related to the MBP Titan subsidiary.

Precigen: Advancing Medicine with Precision

Precigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated unique therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit www.precigen.com or follow us on LinkedIn.

Trademarks

Precigen, UltraPorator, UltraCAR-T, AdenoVerse and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.

On November 9, 2020 UroGen Pharma Ltd. (Nasdaq: URGN), a biopharmaceutical company dedicated to building and commercializing novel solutions that treat specialty cancers and urologic diseases, reported financial results for the third quarter ended September 30, 2020 and provided an overview of the Company’s recent developments (Press release, UroGen Pharma, NOV 9, 2020, View Source [SID1234570324]).

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"We are excited to see the continued interest and uptake of Jelmyto for patients with low-grade upper tract urothelial cancer in the first full quarter of launch, with a steady increase in new patients and providers as well as positive reimbursement trends. Additionally, we are pleased with the feedback we are receiving from urologists who see this treatment as a novel solution to avoid surgical intervention with a positive impact on patient outcomes," said Liz Barrett, President and Chief Executive Officer of UroGen. "With our second product candidate, UGN-102, soon to enter a pivotal trial and a recently enhanced management team, we look forward to continuing our mission of bringing novel solutions to patients with specialty cancers and urologic diseases."

Business Highlights and Upcoming Milestones:

Jelmyto (mitomycin) for pyelocalyceal solution:

Since the June 1, 2020 launch of Jelmyto, the first and only FDA approved non-surgical treatment option for adult patients with low-grade upper tract urothelial cancer (LG-UTUC), the Company has expanded prescriber usage, broadened awareness and increased coverage by commercial plans and Medicare.
As of November 1, 2020, 165 sites have been activated, which means they have completed their internal processes and have treated or are ready to treat patients; 13 sites have treated more than one patient.
The Company has received its C-Code, effective October 1, 2020, and continues to expect receipt of a J-Code in January 2021.
Final durability data from the Phase 3 OLYMPUS pivotal trial evaluating Jelmyto (UGN-101) in LG-UTUC is expected to be presented at a medical meeting by the end of the year.
UGN-102:

Top-line final data from the OPTIMA II Phase 2b trial evaluating UGN-102 in patients with low-grade intermediate risk non-muscle invasive bladder cancer (LG-IR-NMIBC) is expected by the end of the year.
The Company remains on track to initiate ATLAS, a pivotal Phase 3 trial of UGN-102 by year end 2020. The trial will enroll approximately 600 patients and explore UGN-102 as a non-surgical treatment alternative compared to standard of care – transurethral resection of bladder tumor (TURBT) – in patients diagnosed with LG-IR-NMIBC. There are no drugs currently approved by the FDA as first-line treatment for LG-IR-NMIBC, a difficult-to-treat disease with approximately 80,000 addressable patients per year in the U.S. alone.
UGN-302 (UGN-201 (TLR 7/8) + UGN-301 (CTLA-4)):

UroGen expects to commence the Phase I program for UGN-302 in the first half of 2021.
The Company is initially targeting high-grade non-muscle invasive bladder cancer (HG-NMIBC) and has generated encouraging non-clinical data in a murine model suggesting treatment with UGN-201 and a CTLA-4 may result in improved survival and decreased tumor size.
Intravesical delivery may have the potential to mitigate certain systemic side effects and adverse events associated with systemic CTLA-4 antibody administration.
Executive Team Updates:

In September 2020, UroGen announced the appointment of three new executives to the Company’s Executive Leadership Team:
Molly Henderson named Chief Financial Officer
Jason Smith named General Counsel and Chief Compliance Officer
Polly A. Murphy, DVM, Ph.D., named Chief Business Officer
These new leaders bring extensive oncology and industry experience to UroGen, and the Company believes it is well positioned to drive future commercialization growth, pipeline development and platform expansion.
Third Quarter 2020 Financial Results:

Jelmyto Revenue: UroGen reported net product revenue of Jelmyto for the third quarter ended September 30, 2020 of $3.5 million.

R&D Expense: Research and development expenses for the third quarter ended September 30, 2020 were $10.2 million, including non-cash share-based compensation expense of $1.5 million. This compares to $9.5 million, including non-cash share-based compensation expense of $2.1 million, for the same period in 2019. Research and development expenses for the nine months ended September 30, 2020 were $34.9 million, including non-cash share-based compensation expense of $5.0 million. This compares to $29.2 million, including non-cash share-based compensation expense of $6.4 million, for the same period in 2019.

SG&A Expense: Selling, general and administrative expenses for the third quarter ended September 30, 2020 were $22.1 million, including non-cash share-based compensation expense of $5.2 million. This compares to $14.0 million, including non-cash share-based compensation expense of $5.2 million, for the same period in 2019. Selling, general and administrative expenses for the nine months ended September 30, 2020 were $68.1 million, including non-cash share-based compensation expense of $16.5 million. This compares to $40.5 million, including non-cash share-based compensation expense of $15.5 million, for the same period in 2019.

Net Loss: UroGen reported a net loss of $28.8 million, or basic and diluted net loss per ordinary share of $1.31, for the third quarter ended September 30, 2020. This compares to $22.3 million, or basic and diluted net loss per ordinary share of $1.06, for the same period in 2019. UroGen reported a net loss of $98.0 million, or basic and diluted net loss per ordinary share of $4.52, for the nine months ended September 30, 2020. This compares to $66.2 million, or basic and diluted net loss per ordinary share of $3.25, for the same period in 2019.

Cash & Cash Equivalents: As of September 30, 2020, cash, cash equivalents and marketable securities totaled $125.5 million, excluding restricted cash.

2020 Operating Expense Guidance: The Company provided an update to previously issued guidance for 2020. UroGen now expects 2020 total operating expense in the range of $138 to $143 million, including non-cash share-based compensation expense of $25 to $29 million, subject to market conditions. Other non-operating income for 2020 is anticipated to be approximately $2.0 million.

Conference Call & Webcast Information

Members of UroGen’s management team will host a live conference call and webcast today at 8:30 AM Eastern Time to review the Company’s financial results and provide a general business update.

The live webcast can be accessed by visiting the Investors section of the Company’s website at View Source Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. Alternatively, please call (855) 765-5685 (U.S.) or (615) 247-5916 (International) to listen to the live conference call. The conference ID number for the live call will be 2146176. An archive of the webcast will be available for 30 days on the Company’s website.

About Jelmyto

Jelmyto (mitomycin) for pyelocalyceal solution, is a drug formulation of mitomycin indicated for the treatment of adult patients with low-grade upper tract urothelial cancer (LG-UTUC). Utilizing the RTGel technology platform, UroGen’s proprietary sustained release, hydrogel-based formulation, Jelmyto is designed to enable longer exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. Jelmyto is delivered to patients using standard ureteral catheters or nephrostomy tube. The U.S. FDA previously granted Orphan Drug, Fast Track, and Breakthrough Therapy Designations to Jelmyto for the treatment of LG-UTUC. On April 15, 2020, the FDA approved Jelmyto, making it the first drug approved for the treatment of LG-UTUC in adult patients.

About Upper Tract Urothelial Cancer (UTUC)

Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and ten percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as upper tract urothelial cancers (UTUC). In the U.S., there are approximately 6,000 – 7,000 new or recurrent low-grade UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often face comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). These treatments can lead to a high rate of recurrence and relapse.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an investigational drug formulation of mitomycin in Phase 2b development for the treatment of low-grade intermediate risk non-muscle invasive bladder cancer. Utilizing the RTGel Technology Platform, UroGen’s proprietary sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter. The Company reported topline interim results from the Phase 2b OPTIMA II trial in May 2020 and intends to begin a pivotal study to further investigate UGN-102 in the treatment of this condition by year end 2020.

About the Phase 2b OPTIMA II Trial

OPTIMA II (OPTimized Instillation of Mitomycin for Bladder Cancer Treatment) is an open-label, single-arm, multi-center Phase 2b clinical trial of investigational agent UGN-102 (mitomycin) for intravesical solution to evaluate its safety and efficacy in patients with low-grade non-muscle invasive bladder (LG NMIBC) cancer at intermediate risk of recurrence. Intermediate risk is defined as one or two of the following: multiple tumors, solitary tumor >3 cm, or recurrence (≥ 1 occurrence of LG NMIBC within one year of the current diagnosis).

On November 9, 2020 Genocea Biosciences, Inc. (NASDAQ: GNCA), a biopharmaceutical company developing next-generation neoantigen immunotherapies, reported that four posters that collectively validate the company’s unique and differentiated approach to identifying clinically meaningful immunotherapy targets at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting taking place virtually November 9th – 14th (Press release, Genocea Biosciences, NOV 9, 2020, View Source [SID1234570323]).

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GEN-009

In follow up to data shared at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020, the company shared expanded clinical and immunogenicity findings from Part B of its ongoing GEN-009 Phase 1/2a trial, which evaluates GEN-009, Genocea’s neoantigen vaccine, in combination with PD-1 inhibitors in advanced cancers. Posters 390 and 413 outline the clinical and immune responses elicited by GEN-009 in 16 checkpoint inhibitor (CPI) therapy sensitive and resistant patients. Poster 413 was a highly scored abstract selected for a "Poster Walk."

Of the nine CPI-sensitive patients, three patients experienced a novel reduction in tumor volume post-GEN-009 dosing and achieved independent RECIST responses after vaccination, including 2 PRs and 1 CR. Five additional CPI-sensitive patients have shown disease control post-vaccination for up to 11 months. Within the CPI-resistant population, five of seven patients appear to have stabilized disease lasting up to seven months. GEN-009 elicited strong anti-tumor immune responses with both CD4+ and CD8+ T cell responses observed at day 50 post-vaccination and with peak ex vivo responses occurring Day 92. Early data from two patients tested so far show a complete absence of circulating tumor DNA by day 50, which is consistent with a vaccine clinical effect. There was also emerging evidence of epitope spreading in patients who successfully responded to therapy. GEN-009 was safe and well tolerated.

"We are highly encouraged by the response patterns observed in this clinical cohort, which are a novel signal that further support the possibility that GEN-009 administration can significantly decrease tumor burden in certain patients" said Thomas Davis, M.D., Chief Medical Officer of Genocea. "Augmenting the breadth of immune response against relevant cancer specific targets through GEN-009 can deepen CPI response in patients with advanced disease. We will continue to monitor these patients to measure the GEN-009 impact on longer-term disease stabilization. While we await these data, we do not intend to dose additional patients. We believe the

cumulative GEN-009 data set establishes a differentiated clinical profile based on superior neoantigen selection and also provides a strong foundation for GEN-011, which also utilizes ATLAS selected targets to generate a potent cell therapy."

Inhibigens

One distinguishing feature of Genocea’s proprietary ATLAS technology is its ability not only to identify the stimulatory neoantigens to include in GEN-009 and GEN-011, but also to reveal Inhibigens – peptides that elicit T cell responses with the capacity to compromise anti-tumor immunity. Poster 526 delves further into the biology of Inhibigen-specific responses and reveals important insights that add to the company’s growing body of knowledge beyond data previously shared at the AACR (Free AACR Whitepaper) Virtual Annual Meeting II. Findings in mice and humans confirmed the presence of Inhibigens in nearly every sample screened, and mouse data show the abrogation of anti-tumor activity in response to otherwise protective vaccines is associated with decreased CD4+ and CD8+ T cell, macrophage and dendritic cell infiltration into tumors. This outcome may be attributed to abolished cytokine activity in response to tumor-specific vaccine antigens. The data also show that vaccination with an Inhibigen renders CPI co-administration ineffective.

"Our understanding of Inhibigens’ mechanism of action and their translational relevance will be critical as we advance Genocea’s vaccine and adoptive T cell therapy products through the clinic," said Jessica Baker Flechtner, Chief Scientific Officer of Genocea. "Immunotherapies targeting PD-1 and CTLA-4 have become standard of care across multiple cancer indications with remarkable yet variable effects. Learning more about Inhibigen biology may be critical to improving standard-of-care treatments for patients. We believe that Inhibigens must be identified and excluded from the rational design of immunotherapies, including GEN-011, the company’s NPT product."

GEN-011

Poster 149 highlights important advantages of GEN-011 over TIL and TCR-T therapies. GEN-011 has been developed with 100% manufacturing success at clinical scale via PLANET, a process designed to deliver billions of NPTs for every patient. The 16 PLANET runs conducted to date have confirmed GEN-011 comprises over 98% of highly functional, non-exhausted T cells with a mean neoantigen breadth of response nearing 90% of intended targets. In contrast, recent reported data from TIL products showed responses to less than 10% of intended neoantigens. GEN-011 NPTs have an unparalleled breadth of neoantigen coverage, targeting up to 30 relevant antigens. The drug product also avoids pro-tumor Inhibigens that may hinder clinical responses and the PLANET process does not require extra surgery or viable tumor.

"I am pleased by the body of work shared today," said Chip Clark, President and Chief Executive Officer of Genocea. "Our proprietary ATLAS platform has played an integral role in the development of GEN-009 and GEN-011, and we remain eager to continue using ATLAS-based insights to identify both the right targets and Inhibigens to advance these programs in 2021 and beyond."

On November 9, 2020 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported the presentation of data from the melanoma and squamous cell carcinoma of the head and neck (SCCHN) cohorts from the MARIO-1 clinical trial at the SITC (Free SITC Whitepaper) (Press release, Infinity Pharmaceuticals, NOV 9, 2020, View Source [SID1234570322]). MARIO-1 is the Company’s ongoing Phase 1/1b evaluating eganelisib as a monotherapy and in combination with Opdivo (nivolumab) in patients with solid tumors in collaboration with BMS.

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The data presented from the melanoma and SCCHN cohorts of MARIO-1, both which were designed to isolate the clinical benefit of eganelisib by examining clinical activity in patients not expected to benefit from checkpoint inhibitors due to progression on a checkpoint inhibitor as the immediate prior therapy, demonstrate that eganelisib was well tolerated and active, and suggest that greater clinical benefit is achieved in patients who received two or fewer prior lines of therapy.

"These data from the melanoma and SCCHN cohorts of MARIO-1 provide important validation of our mechanism and overall clinical strategy," said Adelene Perkins, Chief Executive Officer and Chair of Infinity Pharmaceuticals. "In addition to establishing a favorable safety profile, we see on-mechanism activity of eganelisib with translational data that show decreased immune suppression as measured by MDSCs as well as increased immune activation during eganelisib treatment. Across these cohorts, we are encouraged by the disease control rate in patients with immediate prior progression on a checkpoint inhibitor, with higher response rates in patients who have received two or fewer prior lines of therapy. These results leave us increasingly confident in our clinical strategy to move eganelisib to earlier treatment settings in our ongoing studies: to the second line in MARIO-275, and to the front-line setting in MARIO-3. Taken together, we are encouraged by these results which suggest eganelisib has the potential to provide meaningful clinical benefits across diverse solid tumors as a first-in-class modulator of immune activity."

Key presentation highlights:

Poster presentation titled, "Updated clinical data from the melanoma expansion cohort of an ongoing Ph1/1bStudy of eganelisib (formerly IPI-549) in combination with nivolumab" presented by Michael Postow, M.D., Chief, Melanoma Service, Memorial Sloan Kettering Cancer Center

Combination treatment with eganelisib and nivolumab was generally well tolerated and associated with a favorable safety profile
Eganelisib in combination with nivolumab demonstrates evidence of clinical activity in patients not expected to benefit from checkpoint inhibitor (CPI) monotherapy due to immediate prior progression on a CPI
Eganelisib in combination with nivolumab achieved a disease control rate (DCR) of 52.6% in 19 patients (10 of 19 patients) and overall response rate (ORR) of 21.1% (4 of 19 patients) in patients with immediate prior progression on CPI therapy and 2 or fewer prior lines of therapies
Translational data validate the on-mechanism eganelisib effect of decreased immune suppression as measured by MDSC levels, and increased immune activation via T Cell reinvigoration, upregulation of IFN-γ responsive factors including CXCL9, CXCL10 and PD-L1
Reversal of progressive disease in patients with immediate prior treatment with anti-PD1/PD-L1 therapy was observed
Oral presentation titled, "Updated clinical data from the squamous cell carcinoma of the head and neck (SCCHN) expansion cohort of an ongoing Ph1/1b Study of eganelisib (formerly IPI-549) in combination with nivolumab" presented by Ezra Cohen, M.D., FRCPSC, FASCO, Medical Oncologist Chief, Division of Hematology-Oncology Associate Director, Translational Science, Moores Cancer Center, UC San Diego Health

Combination treatment with eganelisib and nivolumab was generally well tolerated and associated with a favorable safety profile
Eganelisib in combination with nivolumab demonstrates evidence of clinical activity in patients not expected to benefit from checkpoint inhibitor (CPI) monotherapy due to immediate prior progression on a CPI
Eganelisib in combination with nivolumab achieved a disease control rate (DCR) of 45% in 21 patients (9 of 20 evaluable patients) and overall response rate (ORR) of 10% (2 of 20 evaluable patients) in patients with immediate prior progression on CPI therapy and patients with 2 or fewer prior lines of therapy (n=11) had the greatest clinical benefit with a 20% of patients (2 of 10 evaluable patients) achieving a partial response
Signals of activity in HPV-positive SCCHN tumors were observed with 50% of these patients (n=8) achieving stable disease as compare to 0% of HPV negative patients (n=3)