On March 16, 2021 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) ("Infinity" or the "Company"), a clinical-stage biotechnology company developing eganelisib (IPI-549), a potentially first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic, reported its full year 2020 financial results and provided an update on the Company, including recent progress with eganelisib (Press release, Infinity Pharmaceuticals, MAR 16, 2021, View Source [SID1234576728]).

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"Over the past months, we have presented transformative data across multiple indications, I/O combinations, and lines of therapy which together demonstrate the broad potential of eganelisib to improve upon standard of care therapy across a broad range of treatment settings addressing some of the most challenging unmet needs in oncology," said Adelene Perkins, Chief Executive Officer and Chair of Infinity Pharmaceuticals. "Our data from MARIO-275, a randomized, double-blind, placebo controlled study, clearly demonstrate the benefit of adding eganelisib to nivolumab monotherapy, a standard of care in advanced 2L urothelial cancer, with improved ORR, DCR and PFS as compared to nivolumab monotherapy. Striking benefits were observed in the PD-L1 low patient population, who are underserved by checkpoint inhibitor monotherapy and represent the majority of this patient population. Based on these results, we are planning a registration enabling study in this population.

"Compelling safety and efficacy results presented at SITC (Free SITC Whitepaper), SABCS, and GU ASCO (Free ASCO Whitepaper) suggest that eganelisib may have broad potential to improve outcomes in both PD-L1 low and high patients across tumor types, driven by the immune modulatory mechanism of eganelisib targeting macrophages and other myeloid-derived immune cells," said Brian Schwartz, M.D., consulting Chief Physician of Infinity. "Our initial results from MARIO-3 show that adding eganelisib to an approved front-line regimen in TNBC provide clear patient benefit above standard-of-care atezolizumab and nab-paclitaxel. We observed tumor reductions in 100% of evaluable patients, irrespective of PD-L1 status, and are excited by the broad potential of this novel triplet regimen in both PD-L1 low and high patients given the significant unmet need in this aggressive and difficult-to-treat disease. We look forward to presenting additional data in the first and second half of this year, which will include increased patient numbers, response rate, disease control rate and initial response durability data, with preliminary PFS data by the end of the year. In parallel, the RCC cohort of MARIO-3 continues to advance with data from this proof-of-concept study in a novel triplet regimen expected in the first half of 2022. With our recently strengthened balance sheet, we will continue to advance our development of eganelisib across multiple indications, leveraging data from MARIO-275 in UC, MARIO-3 in TNBC, as well as the ARC-2 data presented by Arcus Biosciences at SABCS in second line TNBC and are evaluating opportunities to further unlock the potential of eganelisib in melanoma and SCCHN from MARIO-1 and in ovarian cancer from the ARC-2 study as we seek to improve outcomes in multiple treatment settings and patient populations including those least likely to respond to immunotherapies."

Recent Updates and Program Guidance:

MARIO-275 and Advanced Urothelial Cancer

Presented positive data from the MARIO-275 randomized, placebo-controlled Phase 2 study evaluating eganelisib in combination with Opdivo in platinum-refractory, I/O naïve patients with advanced urothelial cancer (aUC), in collaboration with Bristol Myers Squibb (BMS) at the 2021 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium
Combination of eganelisib with nivolumab demonstrated improved ORR, DCR, and PFS versus 2L standard of care nivolumab monotherapy
Greatest benefit of eganelisib with nivolumab combination therapy over nivolumab monotherapy was observed in the PD-L1 low patient population (n=23) with improvement over nivolumab monotherapy (n=7) for overall response rate (ORR) (26% vs. 14%); disease control rate (DCR) (57% vs. 14%); and best responses of complete response (CR) (9% vs. 0%), and stable disease (SD) (30% vs. 0%)
PD-L1 low patients demonstrated an extended progression free survival (PFS) with a hazard ratio of 0.54 reflecting a 46% reduction in probability of progression
The combination of eganelisib and nivolumab was well tolerated at the 30mg once daily dose
Translational data support immune modulatory mechanism of action of eganelisib with increased immune activation and decreased immune suppression observed in both the PD-L1 high and low patient populations
Infinity is planning a registration enabling study leveraging findings from MARIO-275. After initial feedback from the U.S. Food and Drug Administration (FDA), additional trial details are expected by the end of Q2 2021, and will likely focus on PD-L1 low aUC patients with a 30 mg QD dose of eganelisib.
MARIO-3 Triple Negative Breast Cancer Cohort

Presented positive data from the ongoing Phase 2 study in collaboration with Roche/Genentech to evaluate eganelisib in a novel triple combination in the front-line setting, adding to the approved doublet of Tecentriq and Abraxane in triple negative breast cancer (TNBC) at the 2020 San Antonio Breast Cancer Symposium
100% of evaluable patients (n=13) demonstrated tumor reduction with a clinical benefit (disease control rate) in 92% of patients (12/13)
69.2% (9/13) overall response rate (ORR) with best responses of complete response (CR) or partial response (PR)
100% (5/5) ORR (CR + PR) with 1 CR and 4 PRs observed in PD-L1 high patients
50% (4/8) ORR (CR + PR) with 4 PRs observed in PD-L1 low patients
The novel triple combination treatment with eganelisib, atezolizumab (atezo) and nab-paclitaxel (nab-pac) demonstrated safety in line with expectations of the component drugs with no additive or new safety signals
Translational data support immune modulatory mechanism of action of eganelisib with increased immune activation and decreased immune suppression observed in both the PD-L1 high and low patient populations
Additional data presentations from the TNBC cohort of MARIO-3 are expected in the first and second half of 2021 with increased patient numbers and early durability data which will include progression free survival in the second half of 2021.
Completion of enrollment is expected in the 2H 2021.
MARIO-3 Renal Cell Carcinoma Cohort

Data from the ongoing, proof-of-concept novel triple combination of eganelisib with Tecentriq and Avastin in the front line setting in renal cell cancer (RCC) are expected in the first half of 2022.
MARIO-1

MARIO-1 melanoma and squamous cell carcinoma of the head and neck (SCCHN) cohorts were designed to isolate the clinical benefit of eganelisib by examining clinical activity in patients not expected to respond to checkpoint inhibitors due to progression following immediately prior checkpoint inhibitor therapy which were presented at the 35th Anniversary Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). The data presented demonstrated that eganelisib had a manageable safety and tolerability profile with ORR ≥ 20% and DCR ≥ 40% in melanoma and SCCHN patients who had progressed on a CPI as their immediate prior therapy after having ≤ 2 prior lines of therapy and support the ongoing strategic prioritization of earlier lines of treatment with eganelisib.
Arcus Collaboration

Data presented at the 2020 San Antonio Breast Cancer Symposium from the Phase 1b collaboration study conducted by Arcus Biosciences, evaluating a checkpoint-inhibitor free, novel triple-combination regimen of eganelisib + etrumadenant (AB928, a dual adenosine receptor antagonist) + Doxil in advanced TNBC patients demonstrated improved activity on top of the doublet therapy of etrumadenant +Doxil. The triplet including eganelisib demonstrated numerical ORR benefit over the doublet in the overall cohort population (42% vs 11%) as well as in the ovarian cancer patient subset (75% vs 14%) and the TNBC patient subset (25% and 9%).
Corporate Update

Significantly strengthened balance sheet with the successful completion in February 2021 of a $92 million public offering with approximately $86 million net proceeds to support execution on the next phase of eganelisib development.
Full Year 2020 Financial Results:

At December 31, 2020, Infinity had total cash, cash equivalents and available-for-sale securities of $34.1 million, compared to $42.4 million at December 31, 2019.
Revenue during 2020 was $1.7 million, which relates to royalties on net sales of Copiktra from Verastem, Inc. and Secura Bio, Inc., who purchased the rights to Copiktra in 2020. Revenue during 2019 was $3.0 million which primarily relates to the achievement of a $2.0 million milestone from PellePharm.
Research and development expense for 2020 was $26.8 million, compared to $27.1 million in 2019.
General and administrative expense was $12.4 million for 2020, compared to $14.3 million for 2019. The decrease in G&A expense in 2020 compared to 2019 was primarily due to a decrease of $0.8 million in compensation, primarily related to a reduction in stock compensation, and a decrease of $0.5 million in professional services.
Net loss for 2020 was $40.5 million, or a basic and diluted loss per common share of $0.68, compared to a net loss of $47.1 million, or a basic and diluted loss per common share of $0.83 for 2019. The decrease in net loss was mostly driven by a decrease in royalty expense in 2020. In 2019, Takeda consented to the sale of the royalties to HealthCare Royalty Partners III, L.P. (HCR) and agreed to forego its rights to an equal share of the royalties due from Secura Bio. In exchange, we paid Takeda $6.7 million representing 25% of the net proceeds from the royalty monetization which we recognized as royalty expense in 2019.
Financial Outlook: Infinity’s 2021 financial guidance, following the closing in February 2021 of a $92 million public offering of Infinity’s common stock is as follows:

Net Loss: Infinity expects net loss for 2021 to range from $40 million to $50 million.
Cash and Investments: Infinity expects to end 2021 with a year-end-cash, cash equivalents and available for sale securities balance ranging from $70 million to $80 million.
Infinity’s financial guidance does not include
additional funding or business development activities, or
a potential $5 million milestone payment from BVF for positive patidegib Phase 3 data and any milestones from, or the sale of the company’s equity interest in, PellePharm
Conference Call Information

Infinity will host a conference call today, March 16, 2021, at 4:30 p.m. ET to discuss these financial results and company updates. A live webcast of the conference call can be accessed in the "Investors/Media" section of Infinity’s website at www.infi.com. To participate in the conference call, please dial (877) 316-5293 (domestic) and (631) 291-4526 (international) five minutes prior to start time. The conference ID number is 7174736. An archived version of the webcast will be available on Infinity’s website for 30 days.

On March 16, 2021 AVEO Oncology (Nasdaq: AVEO) reported financial results for the full year ended December 31, 2020 and provided a business update (Press release, AVEO, MAR 16, 2021, View Source [SID1234576745]).

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"The U.S. Food and Drug Administration’s (FDA) recent approval of FOTIVDA marks a transformative event for AVEO, and we are eager to demonstrate FOTIVDA’s potential to serve as a meaningful new treatment option within the growing relapsed or refractory advanced renal cell carcinoma (RCC) patient population. We look forward to bringing this meaningful new therapy to patients in the U.S. by the end of this month," said Michael Bailey, president and chief executive officer of AVEO. "In parallel, we remain focused on the evaluation of FOTIVDA in the immunotherapy combination setting, with the pivotal Phase 3 TiNivo-2 study of FOTIVDA in combination with OPDIVO expected to commence patient enrollment mid-year."

"We also anticipate notable progress within our clinical programs, with several key inflection points expected to occur in the coming year. This includes a decision on the initiation of a pivotal study of ficlatuzumab in head and neck squamous cell carcinoma (HNSCC), and advancement of our Phase 1 study of AV-380. We look forward to providing updates on our progress in the coming months."

FOTIVDA U.S. Regulatory, Commercial, and IP Updates

FOTIVDA Approved by the FDA for the Treatment of Adult Patients with Relapsed or Refractory Advanced RCC Following Two or More Prior Systemic Therapies. On March 10, 2021, AVEO announced FDA approval of FOTIVDA in the United States for the treatment of adults with relapsed or refractory advanced RCC following two or more prior systemic therapies. FOTIVDA is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). AVEO plans to make FOTIVDA available to patients in the U.S. by March 31, 2021.
Presented New Analyses from the Phase 3 TIVO-3 Study at ASCO (Free ASCO Whitepaper) 2021 GU Cancers Symposium. In February 2021, AVEO presented key subgroup and quality of life analyses from the Phase 3 TIVO-3 study, its pivotal Phase 3 trial comparing tivozanib to sorafenib in RCC patients who are relapsed or refractory to two or more prior therapies, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Genitourinary (GU) Cancers Symposium. The results further demonstrate the benefits of tivozanib over sorafenib. A copy of each presentation is available in the Scientific Publications & Presentations section of AVEO’s website.
Updated IP Strategy Offers Potential for Tivozanib Patent Term Extension to November 2028. AVEO holds an exclusive license to two issued U.S. patents for tivozanib, one pertaining to the tivozanib composition of matter, which expires in April 2022, and the other pertaining to a crystalline form of tivozanib, which expires in November 2023. A patent term extension of up to five years may be available under the Hatch-Waxman Act, although only one patent can be extended under the Act. AVEO currently intends to file applications for patent term extension on both patents in parallel to provide optionality in its exclusivity strategy. Depending upon which patent AVEO ultimately chooses to extend, if a full five-year extension is granted for such patent, tivozanib’s exclusivity period could reach either April 2027 or November 2028.
Tivozanib Immuno-Oncology Updates

Announced Collaboration with Bristol Myers Squibb to Evaluate FOTIVDA in Combination with OPDIVO in Pivotal Phase 3 TiNivo-2 Trial in IO Relapsed or Refractory RCC. In March 2021, AVEO announced that it has entered into a clinical trial collaboration and supply agreement with Bristol Myers Squibb to evaluate FOTIVDA in combination with OPDIVO, Bristol Myers Squibb’s anti-PD-1 therapy, in the pivotal Phase 3 TiNivo-2 trial in patients with advanced relapsed or refractory RCC following prior immunotherapy exposure. Bristol Myers Squibb will provide OPDIVO clinical drug supply for the study. AVEO will serve as the study sponsor and will be responsible for costs associated with the trial execution. AVEO expects to begin enrollment in the trial in mid-2021 subject to FDA feedback on the trial design anticipated in the second quarter of 2021.
Results from Phase 1b Portion of DEDUCTIVE Study in Hepatocellular Carcinoma (HCC) Presented at 2021 ASCO (Free ASCO Whitepaper) GI Cancer Symposium. In January 2021, results from the Phase 1b portion of the Phase 1b/2 DEDUCTIVE clinical trial of tivozanib in combination with IMFINZI (durvalumab), AstraZeneca’s (LSE/STO/Nasdaq: AZN) human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with HCC were presented at the 2021 ASCO (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium. There were no dose-limiting toxicities with the combination. In addition, the combination demonstrated a 29% partial response (PR) rate and 71% disease control rate (PR + stable disease), which is comparable to findings with bevacizumab and TECENTRIQ (atezolizumab), an emerging standard of care in the same setting. Completion of enrollment in the ongoing Phase 2 portion of the study, which is expected to enroll up to an additional 30 subjects, is anticipated later this year.
Results from Phase 1b/2 TiNivo Study of Tivozanib in Combination with OPDIVO (nivolumab) in RCC Published in Annals of Oncology. In November 2020, AVEO announced that previously reported results from the Phase 1b/2 TiNivo study of oral tivozanib in combination with intravenous OPDIVO (nivolumab) , an immune checkpoint, or PD-1, inhibitor, for the treatment of advanced RCC, were published in Annals of Oncology. The article, titled "TiNivo: Safety and Efficacy of Tivozanib-Nivolumab Combination Therapy in Patients with Metastatic Renal Cell Carcinoma", is available online via this link.
Ficlatuzumab Update

Enrollment Complete in Phase 2 Open Label Randomized Study of Ficlatuzumab in HNSCC; Results Expected to Be Presented at a Medical Meeting in Mid-2021; Phase 3 Decision on Track for Mid-2021. In January 2021, AVEO announced completion of enrollment in its randomized confirmatory Phase 2 study of ficlatuzumab as a single agent or in combination with cetuximab, an EGFR-targeted antibody, in metastatic HNSCC patients who have failed prior immunotherapy, chemotherapy and cetuximab (ERBITUX). Ficlatuzumab is AVEO’s potent humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets hepatocyte growth factor (HGF). The study was designed to confirm findings from a Phase 1/2 study of ficlatuzumab and cetuximab where the combination was well tolerated and resulted in a disease control rate of 67%, as well as prolonged progression-free survival and overall survival compared to historical controls.

Results from the Phase 2 study are expected to be presented at a medical meeting in mid-2021. In that timeframe, AVEO plans to announce a Phase 3 decision for ficlatuzumab. In September 2020, AVEO regained full global rights to ficlatuzumab and has initiated clinical manufacture of ficlatuzumab to supply a potential Phase 3 clinical trial in HNSCC, as well as additional potential Phase 2 studies in pancreatic cancer and acute myeloid leukemia.
AV-380 Update

Phase 1 Clinical Study Initiated Following FDA Acceptance of IND Filing. In January 2021, AVEO announced that its Investigational New Drug (IND) application for AV-380, a potent humanized IgG1 monoclonal antibody that targets growth differentiation factor 15 (GDF15), for the potential treatment of cancer cachexia, was accepted by the FDA. A Phase 1 study in healthy subjects has been initiated.
AV-203 Update

Regained Ex-North American Rights to AV-203. In March 2021, AVEO announced it will regain rights to AV-203 outside of North America, its clinical-stage potent humanized IgG1 monoclonal antibody that targets ErbB3 (also known as HER3), following the voluntary termination of its collaboration and license agreement by CANbridge Life Sciences. AVEO will regain rights to AV-203 in all territories globally, and CANbridge has initiated the process to transfer all preclinical data and materials to AVEO.
Corporate Updates

Announced Drawdown of $20 Million Tranche Under $45 Million Debt Facility with Hercules Capital. In March 2021, AVEO announced that it completed a drawdown of $20 million under its previously announced $45 million loan and security agreement with Hercules Capital, Inc. (NYSE: HTGC, Hercules) and its affiliates. With the closing of the second tranche, which was made available in connection with the recent FDA approval of FOTIVDA, AVEO has drawn down a total of $35 million under its loan and security agreement with Hercules. Under the terms of the loan agreement, an additional $10 million will become available if certain sales criteria and other conditions are met.
Announced Appointment of Mike Ferraresso to Chief Commercial Officer. In March 2021, AVEO announced the appointment of Mike Ferraresso to chief commercial officer. He will be responsible for managing AVEO’s commercial strategy and operations, including the commercialization of FOTIVDA. Mr. Ferraresso, who joined AVEO in December 2017, most recently served as AVEO’s senior vice president, business analytics and commercial operations. He has over 20 years of commercial pharmaceutical and biotechnology experience, including 15 years developing and commercializing oncology products.
Announced Appointment of Corinne D. Epperly, MD, MPH to Board of Directors. In January 2021, AVEO announced the appointment of Corinne D. Epperly, MD, MPH, to its Board of Directors. Dr. Epperly brings over 15 years of experience in oncology as a physician and scientist, blending medicine and business with a proven track record in oncology drug development and launches, commercial and medical strategy, marketing, M&A, and operations gained at Iovance Biotherapeutics, VBL Therapeutics, Bristol Myers Squibb, Goldman Sachs, and the National Cancer Institute of the NIH.
Announced Appointment of David Crist as Vice President of Sales. In October 2020, AVEO announced the appointment of David W. Crist as vice president of sales. Mr. Crist, who brings to AVEO over 20 years of oncology sales experience in both launch-stage and late-stage companies, is responsible for building out AVEO’s sales force in preparation for the commercial launch of FOTIVDA in the U.S.
A current summary of AVEO’s activities and corporate updates is available in AVEO’s Corporate Presentation on the Investors portion of AVEO’s website at investor.aveooncology.com.

Full Year 2020 Financial Highlights

AVEO ended 2020 with $61.8 million in cash, cash equivalents, and marketable securities as compared with $47.7 million at December 31, 2019.
Total revenue for 2020 was approximately $6.0 million compared with $28.8 million for 2019, which included the $25.0 million upfront payment in connection with Kyowa Kirin’s buy back of tivozanib non-oncology rights.
Research and development expense for 2020 was $22.7 million compared with $18.0 million for 2019.
General and administrative expense for 2020 was $22.2 million compared with $11.2 million for 2019.
Net loss for 2020 was $35.6 million, or net loss of $1.66 per basic and diluted share, compared with a net income of $9.4 million, or net income of $0.61 per basic and diluted share, in 2019.
Net loss in 2020 reflects an approximate $4.9 million non-cash gain attributable to the decrease in the fair value of the 2016 private placement warrant liability that principally resulted from decreases in the stock price and stock volatility rate that occurred within the fiscal year, as well as a shorter remaining term as the warrants approach expiration. Net income in 2019 reflects an approximate $11.6 million non-cash gain attributable to the decrease in the fair value of the 2016 private placement warrant liability that principally resulted from the decrease in the stock price that occurred within the fiscal year.
Financial Guidance

AVEO believes that its $61.8 million in cash and cash equivalents as of December 31, 2020, along with proceeds from the $20 million drawdown under the Hercules loan facility in March 2021 and from warrant exercises to date, together with anticipated partnership cost sharing reimbursements, royalties from EUSA Pharma (UK) Limited’s (EUSA) FOTIVDA sales, product revenues upon the commercial launch of FOTIVDA in the United States and the potential additional $10 million in credit under the Hercules loan agreement, would allow AVEO to fund planned operations into 2022.

The above guidance estimates the expenses associated with the commercial launch of FOTIVDA in the United States will be approximately $40 million during the year ended December 31, 2021.

About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models1. FOTIVDA was discovered by Kyowa Kirin.

INDICATIONS

FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.
Females and Males of Reproductive Potential: Can impair fertility.
Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.AVEOoncology.com.

About Advanced Renal Cell Carcinoma

According to the American Cancer Society’s 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.2 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,3 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

On March 16, 2021 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics designed to selectively engage and modulate targeted T cells directly within the patient’s body, reported a business update for the fourth quarter and full year 2020 (Press release, Cue Biopharma, MAR 16, 2021, View Source [SID1234608282]).

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"We have executed on our stated corporate goals and objectives for 2020, enabling us to begin 2021 on track, despite the ongoing challenges of the global pandemic. Accordingly, we marked the beginning of 2021 by the dosing of the first patient in our CUE-101 Phase 1 combination trial with KEYTRUDA, which has the potential for significant mechanistic synergies to provide broader patient reach and enhancement of patient benefit," said Dan Passeri, chief executive officer of Cue Biopharma. Mr. Passeri added, "Importantly, we are now well-positioned to execute throughout 2021 with the aim of demonstrating the potential significance of our approach for treating debilitating diseases by restoring immune balance. In oncology, we have the ongoing Phase 1 studies of CUE-101 which aim to establish a potential registration path, as well as proof-of-principle and a mitigated risk profile for the entire CUE-100 series. For autoimmune disease, we remain on-track to demonstrate the potential of deploying our CUE-300 series (partnered with Merck for defined indications) where the autoantigens are known and well characterized, e.g., type 1 diabetes. For autoimmune diseases where the autoantigens are unknown, or not well characterized, we look forward to further progressing our novel CUE-400 series, a recent development that is based on our IL-2 variant and modified TGF-beta."

Ken Pienta, M.D., acting chief medical officer of Cue Biopharma, commented, "We are pleased with the progress and observations made to date in our monotherapy trial and with the initiation of our combination trial of our lead drug candidate CUE-101. We continue to generate supportive clinical datasets from the ongoing dose escalation and expansion portion of the monotherapy trial in preparation for the Phase 1b monotherapy expansion segment of the trial scheduled to begin in the second half of 2021. Furthermore, with the initiation of the combination trial in front-line therapy with KEYTRUDA, combined with the expectation of launching our neo-adjuvant study in newly diagnosed patients later this year, we have implemented a clinical development approach that we believe will enable us to broaden patient reach and maximize the potential for enhancing therapeutic benefit."

Fourth Quarter 2020 Financial Results

The Company reported collaboration revenue of approximately $0.5 million and $1.0 million for the three months ended December 31, 2020 and 2019, respectively. The decrease was primarily due to adjustments in the LG Chem, Ltd. and Merck collaboration budgets and full-time employee allocations.

Research and development expenses were $8.0 million and $7.0 million for the three months ended December 31, 2020 and 2019, respectively. The increase was due to clinical trial activity for the CUE-101 monotherapy and combination clinical trials, hiring of research and development personnel in the fourth quarter of 2020, manufacturing costs for CUE-102 clinical material as well as development of the Neo-STAT cell line.

General and administrative expenses were $3.4 million and $3.1 million for the three months ended December 31, 2020 and 2019, respectively. The increase was due primarily to stock-based compensation and legal fees incurred during the fourth quarter of 2020.

Full Year 2020 Financial Results

The Company reported collaboration revenue of approximately $3.2 million and $3.5 million for the years ended December 31, 2020 and 2019, respectively. The decrease was primarily due to adjustments in the LG Chem Ltd., and Merck collaboration budgets and changes in the allocation of full-time employees to these programs during the year.

Research and development expenses were $33.5 million and $27.5 million for the years ended December 31, 2020 and 2019, respectively. The increase was due to clinical trial activity for the CUE-101 monotherapy and combination clinical trials, hiring of research and development personnel throughout 2020 and manufacturing costs related to CUE-101 and CUE-102 clinical material.

General and administrative expenses were $14.7 million and $12.7 million for the years ended December 31, 2020 and 2019, respectively. The increase in general and administrative expense was due primarily to stock-based compensation and legal fees offset by a decrease in travel expenses as the COVID-19 pandemic continued to hamper business travel throughout 2020.

As of December 31, 2020, the Company had approximately $84.9 million in cash and cash equivalents compared with $59.4 million as of December 31, 2019.

Recent News & Business Updates

Evaluated initial observations in CUE-101 Phase 1 monotherapy dose escalation clinical trial for treatment of HPV+ R/M HNSCC, which demonstrated tolerability and generated encouraging emerging metrics pertaining to pharmacokinetic and pharmacodynamic profile, as well as early signs of anti-tumor activity. Compilation of data to date supports our belief that the Immuno-STAT platform stimulates targeted immune modulation through the selective engagement of disease-relevant T cells.
Dosed the first patient in a Phase 1 dose escalation clinical trial of CUE-101 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), as first-line treatment for HPV+ R/M HNSCC, which is being conducted in parallel at the same clinics that are leading the ongoing Phase 1 monotherapy study of CUE-101.
Extended the term of the research program with Merck under the existing 2017 research collaboration and license agreement toward developing a clinical candidate for the treatment of type 1 diabetes and an additional undisclosed autoimmune disease indication. Under the terms of the extension, Cue Biopharma will receive additional financial research support to further study and develop promising preclinical biologics with the objective of identifying drug product candidates that can be advanced into the clinic.
Presented three posters highlighting the Company’s clinical development and pipeline progress at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 35th Anniversary Annual Meeting (SITC 2020). The posters included a clinical update on CUE-101, the lead drug candidate from the IL-2 based CUE-100 series and data supporting the potential of the Immuno-STAT platform to selectively engage and modulate targeted T cells within the body in a manner that can address a broad range of indications.

On March 16, 2021 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported it has signed an exclusive distribution agreement with Switzerland-based Ewopharma for Piclidenoson in the treatment of psoriasis and Namodenoson in the treatment of liver diseases namely, hepatocellular carcinoma (HCC) the most common form of liver cancer and nonalcoholic steatohepatitis (NASH) (Press release, Can-Fite BioPharma, MAR 16, 2021, View Source [SID1234576703]). Under the terms of the distribution agreement, Ewopharma will pay to Can-Fite $2.25 million upfront with up to an additional $40.45 million payable upon the achievement of regulatory and sales milestones plus 17.5% royalties on net sales. In exchange, Ewopharma will have the exclusive right to market and sell Piclidenoson in Central Eastern European (CEE) countries and Namodenoson in CEE countries and Switzerland. Ewopharma has the right to extend the distribution agreement to new indications that Can-Fite may identify for its drug candidates.

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Ewopharma is a pharmaceutical marketing organization that helps pharma companies access markets in CEE and Switzerland. In addition to Can-Fite, Ewopharma has distribution agreements with many leading healthcare companies worldwide.

"We are very pleased to enter into this distribution agreement with Ewopharma, a leader in pharmaceutical distribution in Eastern Europe. This is a high-value deal that brings Can-Fite non-dilutive funding, and upon regulatory approval, it gives our products immediate access and distribution in the European market," stated Can-Fite VP Business Development Dr. Sari Fishman.

Dr. Shila Schneider, Business Development Manager Ewopharma Group, added, "We are honored to partner with Can-Fite and help bring their innovative and much needed new treatments to patients in our market in Central Eastern Europe and Switzerland. This is a key strategic deal with therapies complementing our portfolio in gastroenterology, oncology and immunology and reinforcing Ewopharma’s long-standing commitment to its entire region."

About Piclidenoson

Piclidenoson is a novel, first-in-class, A3 adenosine receptor agonist (A3AR) small molecule, orally bioavailable drug with a favorable therapeutic index demonstrated in Phase II clinical studies. It is currently being evaluated in a multinational Phase III study as a treatment for moderate to severe psoriasis and a Phase II U.S. study for the treatment of moderate to severe COVID-19.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On March 16, 2021 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs for the treatment of cancer and other life-threatening diseases, reported its financial results for the fourth quarter ended December 31, 2020. As of December 31, 2020, cash, cash equivalents and investments totaled $115.2 million (Press release, Calithera Biosciences, MAR 16, 2021, View Source [SID1234576729]).

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"In the fourth quarter, we maintained a strong cash position and continued to advance our key clinical development programs, including the KEAPSAKE clinical trial evaluating telaglenastat in non-small cell lung cancer in patients with NRF2/KEAP1 genetic mutations, and the Ph1b trial of our arginase inhibitor CB-280 in cystic fibrosis patients," said Susan Molineaux, PhD, president and chief executive officer of Calithera. "We look forward to sharing interim data from the KEAPSAKE trial and the results of the CB-280 trial in cystic fibrosis patients, each in the second half of 2021."

Fourth Quarter 2020 and Recent Highlights

Announced top-line results of randomized CANTATA trial of telaglenastat with cabozantinib in advanced renal cell carcinoma (RCC). The Phase 2 CANTATA trial is a global, randomized, double-blind clinical trial of telaglenastat combined with cabozantinib, in patients with advanced or metastatic RCC who have received one or two prior treatments. On January 4, 2021, Calithera announced topline results from the CANTATA clinical study and reported the trial did not meet the primary endpoint of improving progression free survival (PFS) in the study population.
Continued enrollment of the Phase 2 randomized KEAPSAKE trial in non-small cell lung cancer (NSCLC) patients with genetic mutation NRF2/KEAP1. The double-blind KEAPSAKE trial will enroll approximately 120 patients with stage IV non-squamous NSCLC with tumors that have the KEAP1 or NRF2 mutation. Patients will be randomized to receive telaglenastat or placebo, in combination with pembrolizumab, carboplatin and pemetrexed. The study will evaluate the safety and investigator-assessed progression-free survival (PFS) of telaglenastat plus this standard-of-care chemoimmunotherapy regimen. Calithera anticipates sharing interim data from the KEAPSAKE trial in the second half of 2021.
Initiated a Phase 1b clinical trial of CB-280 in patients with cystic fibrosis. In October, Calithera presented a trial in progress poster at the North American Cystic Fibrosis 2020 Virtual Conference. The presentation included preclinical study results which suggest CB-280 significantly improved lung function and reduced Pseudomonas aeruginosa colony-forming units in pre-clinical models. Arginase inhibition with CB-280 resulted in improved central airway resistance in CFTR knockout mice, and decreased lung infection in wild type and DeltaF508-CFTR-expressing mice infected with Pseudomonas aeruginosa. Enrollment in the Ph1b study is ongoing and Calithera expects to share data in the second half of 2021. In November 2020, Calithera was awarded up to $2.4M from the Cystic Fibrosis Foundation to support clinical development of CB-280.

Presented preclinical data for CB-668 IL4I1 program at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November. CB-668 is a potent, selective, small-molecule, oral inhibitor of IL4I1, an amino acid oxidase that inhibits anti-tumor immunity and promotes tumor growth. IL4I1 regulates several aspects of adaptive immunity, including inhibition of cytotoxic T cells through its production of both hydrogen peroxide and activators of the aryl hydrocarbon receptor. CB-668 increases pro-inflammatory gene expression in tumors leading to an anti-tumor effect in mouse tumor models.
Selected Fourth Quarter and Full Year 2020 Financial Results

Cash, cash equivalents and investments totaled $115.2 million at December 31, 2020, which management believes will be sufficient to meet its current operating plan through 2022.

Research and development expenses for the full year 2020 were $71.0 million, compared to $76.3 million in the prior year. The decrease of $5.3 million was due to a $6.2 million decrease in the INCB001158 program and a $3.8 million decrease in early-stage research programs, partially offset by an increase of $2.7 million in the telaglenastat program and an increase of $2.0 million in the CB-280 program. Research and development expenses for the fourth quarter of 2020 were $17.1 million, compared to $17.9 million for the same period last year.

General and administrative expenses for the full year 2020 were $20.4 million, compared to $16.6 million in the prior year. The increase of $3.8 million was primarily related to a $2.5 million increase in personnel-related and facility costs and a $1.3 million increase in professional services costs. General and administrative expenses for the fourth quarter of 2020 were $5.6 million, compared to $4.6 million for the same period last year.

Interest and other income, net for the full year 2020 was $1.3 million, compared to $3.0 million in the prior year, mainly as a result of lower interest rates. Interest and other income, net for the fourth quarter of 2020 was $0.1 million, compared to $0.7 million for the fourth quarter of 2019.

Net loss for the three months and year ended December 31, 2020, was $22.6 million and $90.1 million, respectively.

Conference Call Information

Calithera will host an update conference call today, Tuesday, March 16, at 5:00 p.m. Eastern Time/2:00 p.m. Pacific Time. The call may be accessed by dialing (855) 783-2599 (domestic) or (631) 485-4877 and referring to conference ID 6250035. To access the live audio webcast or the subsequent archived recording, visit the Investors section of the Calithera website at www.calithera.com. The webcast will be recorded and available for replay on Calithera’s website for 30 days.