On March 11, 2021 BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), reported the publication of proof-of-concept data on a novel, fully human FcγRIIB-blocking antibody, BI-1607, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, being held virtually April 10-15 and May 17-21 (Press release, BioInvent, MAR 11, 2021, View Source,c3303983 [SID1234576469]).

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"The data on BI-1607 are very exciting and provide proof-of-concept of its ability to enhance anti-cancer immunity, illustrated by its ability to boost activity and overcome resistance to CTLA-4-based therapy," said Martin Welschof, CEO of BioInvent. "We are looking forward to advancing BI-1607 into clinical development and expect to submit a clinical trial application during H2 2021. It will be BioInvent’s fourth drug candidate in clinical development, further demonstrating the strength and productivity of our technology platform."

Understanding mechanisms and overcoming resistance to distinct classes of antibody drugs has the potential to further improve cancer outcomes, explains the AACR (Free AACR Whitepaper) abstract, entitled "A novel FcγRIIB-blocking antibody to enhance FcγR-dependent antitumor immunity". BI-1607 has a novel mechanism-of-action and is designed to enhance FcγR-dependent antitumor immunity. The abstract outlines how BI-1607 enhances the therapeutic activity of anti-CTLA-4 in responsive (MC38) or resistant (CT26) experimental disease models (syngeneic immune competent) and that a triple combination – of BI-1607, anti-PD-1 and low dose anti-CTLA-4 – significantly enhanced survival in a B16 tumor model not responsive to checkpoint blockade. For further information and access to the full abstract, visit View Source!/9325/presentation/2743.

BioInvent’s lead compound BI-1206, evaluated in two separate Phase I trials for hematological or solid tumors, is one of three ongoing drug candidates in clinical development. The company initiated a Phase I/IIa trial of anti-TNFR2 antibody BI-1808 in January 2021 and a Phase l/lla trial of the novel oncolytic vaccinia virus BT-001, together with partner Transgene, in March 2021.

On March 11, 2021 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported the submission of a New Drug Application (NDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) for enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer that has progressed after anti-cancer medication (Press release, Astellas Pharma, MAR 11, 2021, View Source [SID1234576468]). If approved, enfortumab vedotin would be the first antibody-drug conjugate (ADC) available in Japan for people living with this form of urothelial cancer.

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The submission is based on two global clinical trials with sites in Japan. The Phase 3 EV-301 trial evaluated enfortumab vedotin versus chemotherapy in adult patients with locally advanced or metastatic urothelial cancer who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. The Phase 2 EV-201 trial evaluated enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy and who are ineligible for cisplatin (cohort 2).1,2

Enfortumab vedotin met the primary endpoints of overall survival (EV-301) and confirmed objective response rate per blinded independent central review (EV-201).3,4,5

"More than 24,000 people in Japan are diagnosed with urothelial cancer each year. For those whose cancer progresses despite treatment with chemotherapy and immunotherapy, there is no standard treatment option currently," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "Based on data from two global clinical trials, and following the Ministry of Health, Labour and Welfare’s review, enfortumab vedotin may offer a new option for these patients."

About Urothelial Cancer
Urothelial cancer is the most common type of bladder cancer (90 percent of cases), and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.6 Globally, approximately 549,000 new cases of bladder cancer and 200,000 deaths are reported annually.7 In Japan, it is estimated that 24,300 patients are diagnosed with this form of cancer and 9,500 deaths are reported annually.8

Locally advanced and metastatic urothelial cancer is an aggressive disease that is associated with poor survival and high healthcare costs.9 Five-year relative survival rates for metastatic disease are estimated to be approximately 7 percent.10

About the EV-301 Trial
The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician’s choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1 or PD-L1 inhibitor and platinum-based therapies.1 The primary endpoint is overall survival of participants treated with enfortumab vedotin compared to those treated with chemotherapy. Secondary endpoints include progression-free survival, duration of response, and overall response rate, as well as assessment of safety/tolerability and quality-of-life parameters. Results of the EV-301 trial were published in the New England Journal of Medicine.

About the EV-201 Trial
The EV-201 trial (NCT03219333) is a single-arm, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally.2 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability. Results of the first cohort from the EV-201 trial were published in The Journal of Clinical Oncology and results from the second cohort were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancer Symposium.

About Enfortumab Vedotin
Enfortumab vedotin is an antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.11,12 Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).11

About the Astellas and Seagen Collaboration
Astellas and Seagen Inc. are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration. In the United States, Astellas and Seagen co-promote enfortumab vedotin under the brand name PADCEV (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings.

On March 11, 2021 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that an abstract for a poster presentation at the AACR (Free AACR Whitepaper) (American Association for Cancer Research) Annual Meeting 2021, presenting new preclinical data for the clinical asset mitazalimab, is now released (Press release, Alligator Bioscience, MAR 11, 2021, View Source [SID1234576467]). The AACR (Free AACR Whitepaper) Annual Meeting 2021 will be held in a virtual format over two one-week periods in April and May 2021. Alligator Bioscience’s abstract will be presented in an ePoster session during April 10-15.

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Alligator Bioscience has previously shown that mitazalimab synergizes effectively with immune checkpoint inhibitors and vaccines. The abstract, titled "Mitazalimab, a potent CD40 agonist with potential for combination with chemotherapy", demonstrates that mitazalimab synergizes with chemotherapy, notably FOLFIRINOX, leading to improved long-term survival in a preclinical tumor model.

"The new preclinical data are very encouraging. Together with the clinical data of mitazalimab from a previous Phase I study, where mitazalimab was well tolerated up to 1200 µg/kg, these data support the upcoming clinical Phase II study of mitazalimab in combination with chemotherapy in pancreatic cancer patients," says Per Norlén, CEO of Alligator Bioscience.

Mitazalimab is a human CD40 agonistic antibody developed for immunotherapy of cancer. The chemotherapy cocktail FOLFIRINOX kills tumor cells leading to increased release of tumor antigens. Activation of CD40 leads to improved presentation of tumor antigens, and the consequent T cell priming and initiation of T cell-dependent anti-tumor responses.

On March 11, 2021 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, reported financial results for the fourth quarter and year ended December 31, 2020 (Press release, RAPT Therapeutics, MAR 11, 2021, View Source [SID1234576455]).

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"In 2020, we achieved important advancements in clinical development for our two lead programs: FLX475 in oncology and RPT193 in inflammatory diseases," said Brian Wong, M.D., Ph.D., President and Chief Executive Officer of RAPT Therapeutics. "In November, we reported early evidence of clinical activity for FLX475, both as monotherapy and in combination with pembrolizumab, in multiple tumor types. These data helped us determine advancement of several cohorts in our multi-cohort, multi-indication Phase 1/2 trial. For RPT193, we continued enrolling our Phase 1b study of RPT193 in atopic dermatitis over the course of 2020 despite a brief pause early in the year because of the pandemic. Today, we are well positioned for key data readouts for both RPT193 and FLX475. We plan to report on the Phase 1b trial for RPT193 in the first half of 2021 and provide an update in the second half of 2021 on additional data generated with FLX475 in multiple cohorts that have sufficiently matured."

Financial Results for the Fourth Quarter and Year Ended December 31, 2020

Fourth Quarter Ended December 31, 2020
Net loss for the fourth quarter of 2020 was $12.7 million, compared to $13.2 million for the fourth quarter of 2019.

Research and development expenses for the fourth quarter of 2020 were $10.9 million, compared to $10.2 million for the same period in 2019 due to increased clinical trial costs for FLX475 and RPT193, increased personnel costs and stock-based compensation expense and an increase in preclinical program costs, offset by a decrease in laboratory supplies spend.

General and administrative expenses for the fourth quarter of 2020 were $3.5 million, compared to $2.6 million for the same period of 2019. The increase was primarily due to increases in stock-based compensation expense, personnel costs, legal and accounting fees and insurance expense, offset by a decrease in consulting costs.

Year Ended December 31, 2020
Net loss for the year ended December 31, 2020 was $52.9 million, compared to $43.0 million for the same period in 2019.

Research and development expenses for the year ended December 31, 2020 were $45.5 million, compared to $34.9 million for the same period in 2019. The increase was primarily due to an increase in clinical trial costs relating to FLX475 and RPT193, increased preclinical program costs as well as increases in stock-based compensation and personnel expenses, offset by decreases in lab supplies and travel costs.

General and administrative expenses for the year ended December 31, 2020 were $12.8 million, compared to $8.7 million for the same period of 2019. The increase in general and administrative expenses was primarily due to increases in stock-based compensation expense, personnel costs and costs associated with our public company status, offset by a decrease in professional fee and travel costs.

As of December 31, 2020, the Company had cash and cash equivalents and marketable securities of $111.5 million.

On March 11, 2021 Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses, reported recent business highlights and financial results for the fourth quarter and year ended December 31, 2020 (Press release, Selecta Biosciences, MAR 11, 2021, View Source [SID1234576454]).

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"This is a very exciting time in Selecta’s history, having made significant progress across all aspects of the company," said Carsten Brunn, Ph.D., president and chief executive officer of Selecta. "In 2020, we significantly de-risked the company through a strategic partnership with Sobi for SEL-212, under which we commenced the Phase 3 DISSOLVE program in the third quarter of 2020. We rapidly advanced our pipeline, having recently dosed our first subject with ImmTOR in combination with an AAV capsid, which builds on compelling non-human primate data announced earlier this year."

"We are very pleased by the continued progress of our gene therapy program. In collaboration with AskBio, our lead program in methylmalonic acidemia, is on track to enter the clinic in the second quarter of this year and we expect initial data by the end of the year. A key objective of 2021 will be to generate human data in our gene therapy programs and to continue to build our extensive pipeline in gene therapies, enzyme therapies—with an expected IND filing by the end of the year in IgA nephropathy—and autoimmune diseases, as we work to deliver on our mission to leverage our pioneering ImmTOR platform to improve the lives of patients and their families," Dr. Brunn added.

Recent Business Highlights and Anticipated Milestones

Enzyme Therapies:

SEL-212 for chronic refractory gout: The Phase 3 DISSOLVE clinical program for SEL-212 for the treatment of chronic refractory gout, which was licensed to Sobi, is progressing as planned with topline data expected in the second half of 2022.
The Phase 3 clinical program consists of two double blind, placebo-controlled trials of SEL-212 (DISSOLVE I and DISSOLVE II) (NCT04513366 and NCT04596540, respectively). Both studies have a 6-month primary endpoint of serum uric acid (SUA) < 6 mg/dL at month 6, and DISSOLVE I has a 6-month safety extension.
IgA nephropathy: Selecta’s second indication is IgA nephropathy, a kidney disease that occurs when immune complexes of an antibody called immunoglobulin A1 (IgA1) accumulates in the kidneys. Leveraging the learnings from SEL-212, Selecta will be researching a novel therapeutic approach by combining ImmTOR with an enzyme, IgA1 protease, which has been shown in animal studies to debulk the IgA1 immune complexes in the kidney, the root cause of IgA nephropathy. Selecta expects to file an Investigational New Drug, or IND, application, for this program by the end of 2021.
Gene Therapies:

MMA-101 for methylmalonic acidemia (MMA): Selecta’s lead gene therapy product candidate, MMA-101 combined with ImmTOR for the treatment of MMA, is expected to enter the clinic in the second quarter of 2021 with preliminary data expected by year-end. The MMA-101 program is being conducted in collaboration with AskBio.
Selecta and AskBio received Orphan Designation for MMA-101 from the U.S. Food and Drug Administration (FDA) in November 2020. MMA-101 previously received Rare Pediatric Disease Designation from the FDA in October 2020.
First-in-human trial of SEL-399: In collaboration with AskBio, Selecta recently initiated the first-in-human dose-escalation trial of SEL-399, an adeno-associated viral serotype 8 (AAV8) empty vector capsid (EMC-101) containing no DNA combined with ImmTOR. The trial aims to determine the optimal dose of ImmTOR to mitigate the formation of antibodies to AAV8 capsids used in gene therapies. Selecta and AskBio expect to report initial data in the fourth quarter of 2021.
The dose-escalation trial of SEL-399 is designed to evaluate the safety and preliminary efficacy of ImmTOR in combination with an AAV capsid. Preliminary efficacy will be measured by assessing levels of AAV8-specific neutralizing antibodies.
SEL-313 for ornithine transcarbamylase deficiency (OTC deficiency): Selecta’s proprietary gene therapy product candidate, SEL-313, is being developed to treat OTC deficiency, a rare genetic disorder that causes ammonia to accumulate in the blood due to mutations in the OTC gene, which is critical for proper function of the urea cycle. SEL-313 is currently in preclinical development and is expected to enter the clinic in 2022. A Pediatric Investigation Plan (PIP) for SEL-313 was submitted to the European Medicines Agency (EMA) pediatric committee in February 2021.
Non-human primate data of ImmTOR in gene therapy: Selecta’s gene therapy programs build on extensive preclinical data that have demonstrated the potential benefits of the ImmTOR platform in AAV gene therapy. Selecta observed that co-administration of AAV vector and ImmTOR in non-human primates (NHP) enabled higher and more durable transgene expression as well as robust inhibition of anti-AAV8 immunoglobulin G (IgG) and neutralizing antibodies.
Restoring Self-Tolerance in Autoimmune Diseases:

Selecta continues IND-enabling work on an ImmTOR-based approach to treating primary biliary cholangitis (PBC), a chronic, progressive liver disorder that leads to inflammation, damage and scarring of the small bile ducts. PBC has a well-defined target antigen, significant unmet medical need, and is well suited to the application of our ImmTOR immune tolerance platform. Selecta expects to file an IND in PBC in 2022.
Fourth Quarter and Full Year 2020 Financial Results:

Cash Position: Selecta had $140.1 million in cash, cash equivalents, and restricted cash as of December 31, 2020, which compares to cash, cash equivalents, and restricted cash of $147.6 million as of September 30, 2020. Selecta believes its available cash, cash equivalents, and restricted cash will be sufficient to meet its operating requirements into the second quarter of 2023.

Revenue: Revenue recognition for the fourth quarter and fiscal year 2020 was $12.0 million and $16.6 million, respectively, which compares with $6.7 million and $6.7 million for the same periods in 2019.

Revenue was primarily driven by the license agreement with Sobi resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program.

Research and Development Expenses: Research and development expenses for the fourth quarter and fiscal year 2020 were $15.1 million and $54.5 million, respectively, which compares with $15.2 million and $42.7 million for the same periods in 2019.

During the quarter ended December 31, 2020, there was a reduction in expenses for the SEL-212 clinical programs due to the timing of the initiation of the Phase 3 DISSOLVE clinical program compared to the Phase 2 COMPARE program in the prior period. This reduction was offset by increases in expenses incurred under the AskBio Collaboration combined with internal research and development to support our clinical programs. The annual increase reflects the initiation of the Phase 3 DISSOLVE clinical program. These costs are subject to the cost reimbursement arrangement under the license agreement with Sobi.

General and Administrative Expenses: General and administrative expenses for the fourth quarter and fiscal year 2020 were $4.8 million and $18.9 million, respectively, which compares with $4.1 million and $16.4 million for the same period in 2019. The quarterly and annual increase in expense was the result of increased patent and professional fees and facility and office expenses offset by a decrease in travel expense.

Net Loss: For the fourth quarter and fiscal year 2020, Selecta reported a net loss of $15.4 million, or $0.14 per share and $68.9 million, or $0.68 per share, respectively, compared to a net loss of $14.9 million, or $0.28 per share and $55.4 million, or $1.22 per share, for the same periods in 2019.

Conference Call and Webcast Reminder:
Selecta management will host a conference call at 8:30 AM ET today to provide a corporate update and review the company’s fourth quarter 2020 financial results. Individuals may participate in the live call via telephone by dialing (844) 845-4170 (domestic) or (412) 717-9621 (international) and may access a teleconference replay for one week by dialing (877) 344-7529 (domestic) or (412) 317-0088 (international) and using confirmation code 10147796. Investors and the public can access the live and archived webcast of this call and a copy of the presentation via the Investors & Media section of the company’s website, www.selectabio.com.