On May 10, 2021 AVEO Oncology (Nasdaq: AVEO), a commercial and clinical development stage biopharmaceutical company, reported financial results for the first quarter ended March 31, 2021 and provided a business update (Press release, AVEO, MAY 10, 2021, View Source [SID1234579544]).

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"The first quarter of 2021 was a transformational time for AVEO marked by the U.S. Food and Drug Administration (FDA) approval and launch of FOTIVDA, our first commercial product, and the advancement of our pipeline, all of which is supported by a strong balance sheet," said Michael Bailey, president and chief executive officer of AVEO. "Our sales team is now fully deployed, and we are encouraged by the early commercial activity supporting the FOTIVDA launch. We look forward to continuing to execute on our goal of establishing FOTIVDA as a standard of care within its renal cell carcinoma (RCC) indication."

"In parallel, we remain focused on the continued advancement of the remainder of our clinical programs. This includes the evaluation of FOTIVDA in the immunotherapy combination setting, with patient enrollment in the pivotal Phase 3 TiNivo-2 study of FOTIVDA in combination with OPDIVO anticipated to commence mid-year and the Phase 2 hepatocellular carcinoma (HCC) DEDUCTIVE trial reporting encouraging Phase 1b results at ASCO (Free ASCO Whitepaper) GI earlier this year. Beyond FOTIVDA, we continue to expect several key inflection points with the balance of our clinical pipeline later this year, including a go/no go decision on progressing to a pivotal study for ficlatuzumab in head and neck squamous cell carcinoma (HNSCC), the advancement of our Phase 1 study of AV-380 and an update on potential clinical development plans for AV-203."

FOTIVDA U.S. Regulatory and Commercial Updates

U.S. Commercial Launch Underway Following FDA Approval of FOTIVDA for the Treatment of Adult Patients with Relapsed or Refractory Advanced RCC Following Two or More Prior Systemic Therapies.
Announced FDA approval of FOTIVDA for the treatment of adults with relapsed or refractory advanced RCC following two or more prior systemic therapies on March 10, 2021.
Net product revenue for the first quarter of 2021 was $1.1 million, which reflects inventory shipped to distributors and a 15.0% gross to net estimate in the last week of March as FOTIVDA became commercially available on March 22, 2021.
All distributors that made orders in the first quarter have placed reorders for the second quarter.
As of April 30, 2021, 49 prescriptions have been filled and 75 samples have been requested and delivered.
In March 2021, AVEO announced that the National Comprehensive Cancer Network updated its Clinical Practice Guidelines to include FOTIVDA as a recommended regimen for subsequent therapy.
Tivozanib Clinical Updates

Additional Data from the TIVO-3 Study to be Presented at 2021 ASCO (Free ASCO Whitepaper) Annual Meeting in June 2021. Additional data from the TIVO-3 study will be featured during two poster presentations at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)(ASCO) Annual Meeting in June 2021. The presentations, titled "TIVO-3: Durability of response and updated overall survival of tivozanib versus sorafenib in metastatic renal cell carcinoma (mRCC)" and "Temporal characteristics of treatment-emergent adverse events and dose modifications with tivozanib and sorafenib in the phase 3 TIVO-3 study of relapsed or refractory mRCC", will be featured on Friday, June 4.
Announced a Collaboration with Bristol Myers Squibb to Evaluate FOTIVDA in Combination with OPDIVO in a Planned Pivotal Phase 3 TiNivo-2 Trial in IO Relapsed or Refractory RCC. In March 2021, AVEO announced that it entered into a clinical trial collaboration and supply agreement with Bristol Myers Squibb (NYSE: BMS) to evaluate FOTIVDA in combination with OPDIVO, Bristol Myers Squibb’s anti-PD-1 therapy, in the planned 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 recently received feedback from the FDA on the trial design and expects to commence enrollment in the trial in mid-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 at the ASCO (Free ASCO Whitepaper) 2021 Genitourinary (GU) Cancers Symposium. The results further demonstrate the potential tolerability benefits of tivozanib. A copy of each presentation is available in the Scientific Publications & Presentations section of AVEO’s website.
Results from Phase 1b Portion of DEDUCTIVE Study in 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, 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 recorded in the DEDUCTIVE trial. In addition, the combination demonstrated a 29% partial response (PR) rate and a 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.
Ficlatuzumab Clinical Update

Enrollment Complete in Phase 2 Open Label Randomized Study of Ficlatuzumab in HNSCC; Results Expected to Be Presented at ASCO (Free ASCO Whitepaper) in June 2021; Phase 3 Go/No Go Decision Anticipated 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 (ERBITUX), an EGFR-targeted antibody, in metastatic HNSCC patients who have failed prior immunotherapy, chemotherapy and cetuximab. 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 in a poster discussion at ASCO (Free ASCO Whitepaper) in June 2021. Following the ASCO (Free ASCO Whitepaper) data presentation, AVEO plans to announce a go/no go Phase 3 decision for ficlatuzumab in HNSCC.

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 Clinical Update

Phase 1 Clinical Study Initiated Following FDA Acceptance of IND Filing. Recently, AVEO initiated enrollment for a Phase 1 study of AV-380, a potent humanized IgG1 monoclonal antibody that targets growth differentiation factor 15 (GDF15), for the potential treatment of cancer cachexia.
AV-203 Clinical Update

To Regain 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. The Company expects to provide an update on the AV-203 clinical development plan in the second half of 2021.
Corporate Updates

Strong Balance Sheet to Support U.S. Launch of FOTIVDA. In the first quarter of 2021, AVEO added approximately $78.1 million to its balance sheet, consisting of a $20.0 million drawdown under its previously announced $45.0 million loan and security agreement with Hercules Capital. Inc. (NYSE: HTGC, Hercules), $3.1 million from warrant exercises as of March 31, 2021, $3.4 million in stock sales under its at-the-market sales agreement with SVB Leerink LLC and $51.6 million in net proceeds from a public offering of its common stock.
Strengthened Board of Directors with Two New Appointments. AVEO has recently announced the appointments of Kevin Cullen, M.D., and Corinne D. Epperly, M.D., MPH, to its Board of Directors.

Dr. Cullen, a widely recognized clinical oncologist with a specialty in head and neck cancer, is the Marlene and Stewart Greenebaum Distinguished Professor in Oncology and director of the Program in Oncology at the University of Maryland School of Medicine. He also serves as director of the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center.

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.
Appointment of Mike Ferraresso to Chief Commercial Officer. In March 2021, AVEO announced the appointment of Mike Ferraresso to chief commercial officer. He is 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.
First Quarter 2021 Financial Highlights

AVEO ended Q1 2021 with $121.4 million in cash, cash equivalents and marketable securities as compared with $61.8 million at December 31, 2020.
Total revenue for Q1 2021 was approximately $1.9 million compared with $0.8 million for Q1 2020.
Research and development expense for Q1 2021 was $5.8 million compared with $7.8 million for Q1 2020.
Selling, general and administrative expense for Q1 2021 was $15.1 million compared with $3.7 million for Q1 2020.
Net loss for Q1 2021 was $22.1 million, or net loss of $0.81 per basic and diluted share, compared with a net loss of $8.4 million for Q1 2020, or net loss of $0.52 per basic and diluted share.
Net loss for Q1 2021 reflects an approximate $2.4 million non-cash loss attributable to the increase in the fair value of the 2016 private placement warrant liability that principally resulted from increases in the stock volatility rate that occurred within the first quarter, as well as a shorter remaining term as the warrants approach expiration. Net loss in Q1 2020 reflects an approximate $2.6 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 $121.4 million in cash and cash equivalents as of March 31, 2021, along with net product revenues from the commercial launch of FOTIVDA in the United States, would enable AVEO to maintain its current operations for a period of at least 12 months following the filing of its Quarterly Report on Form 10-Q.

AVEO expects commercial spend will be approximately $40 million for the year. Gross margins are expected to be in the mid-to-high 80th percentile and research and development expense is expected to be approximately $40 million for existing pipeline plans during 2021. In addition, quarterly general and administrative expense should approximate the level seen during the first quarter of this year.

Conference Call and Webcast

In connection with this announcement, AVEO will host a conference call and audio webcast today, May 10, 2021, at 4:30 PM Eastern Time. The call can be accessed by dialing (844) 882-7841 (U.S. and Canada) or (574) 990-9828 (international). The passcode for the conference call is 3996993. To access the live webcast, or the subsequent archived recording, please visit the Investors section of the AVEO website at www.aveooncology.com.

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 models.1 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.FOTIVDA.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 May 10, 2021 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported financial results for the first quarter ended March 31, 2021 and provided a business update (Press release, Mersana Therapeutics, MAY 10, 2021, View Source [SID1234579571]).

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"The recent initiation of UPLIFT, a single-arm registrational strategy evaluating UpRi in platinum-resistant ovarian cancer, speaks to the team’s commitment to achieving key milestones and dedication to developing therapies for people living with cancer. We believe UpRi has demonstrated promising activity and a differentiated tolerability profile in studies to date in patients with heavily-pretreated ovarian cancer and limited options. UPLIFT has been designed to increase the potential for label differentiation, speed to market, and the probability of success. We also remain on track to initiate the UPGRADE umbrella combination study in the third quarter of 2021 as a first step in bringing UpRi to patients in earlier lines of therapy and establishing UpRi as a foundational medicine in ovarian cancer," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "We are excited to continue this productive year by building out our maturing pipeline of innovative ADC candidates with the potential to address unmet medical needs across multiple different tumor types."

Recent Highlights and Anticipated Milestones

Upifitamab Rilsodotin (UpRi, previously XMT-1536), first-in-class Dolaflexin ADC targeting NaPi2b:

Initiated UPLIFT, a single-arm registration strategy in platinum-resistant ovarian cancer. In April 2021, the Company announced the initiation of patient dosing in UPLIFT, a single-arm registration strategy evaluating the safety and efficacy of UpRi in patients with platinum-resistant ovarian cancer who have received up to four lines of therapy. Consistent with the bevacizumab label, patients previously treated with three or four lines of therapy may enroll without regard to prior bevacizumab treatment. There is no exclusion for patients with baseline peripheral neuropathy. Patients may enroll without regard to NaPi2b expression; however, the role of the biomarker will be evaluated. The primary endpoint will be the objective response rate (ORR) in the high NaPi2b population and the secondary endpoints will be the ORR regardless of NaPi2b expression, as well as duration of response and safety. UPLIFT is an amendment to the ongoing multinational, multi-center, open label study protocol, and the Company expects to enroll approximately 100 patients with high NaPi2b expression and up to 180 patients overall.

In April 2021, the Company announced its plans to use Tumor Proportion Score (TPS) greater than or equal to 75% as the predefined threshold for high NaPi2b expression in UPLIFT. In the ovarian cancer expansion study data presented to date, TPS ≥ 75% resulted in an objective response rate (ORR) of 39% in high NaPi2b patients relative to an ORR of 28% in the overall population. As part of its diagnostic development plan, the Company evaluated TPS methodology in the expansion portion of the Phase 1 study in ovarian cancer and demonstrated that TPS captures a broad dynamic range of expression values, enriches for response, and offers reproducibility advantages across commercial labs. The Company also disclosed the steps it has taken to develop a robust, predictive and reproducible commercial diagnostic assay which will be used in a prospectively defined retrospective analysis in UPLIFT.

UPGRADE combination dose escalation umbrella study in ovarian cancer expected to initiate in the third quarter of 2021. The Company plans to initiate the UPGRADE study in the third quarter of 2021 to evaluate the combination of UpRi with other agents, starting with a platinum combination. The Phase 1, open-label, dose-escalation portion of the study will determine the maximum tolerated dose (MTD) and safety and tolerability of a once-every-four-week (Q4W) administration of UpRi in combination with Q4W administration of carboplatin for six cycles followed by UpRi monotherapy in platinum-sensitive patients with high-grade serous ovarian cancer who have received 1-2 prior platinum-based regimens. Patients will not be preselected for NaPi2b expression; however, archival or fresh tissue will be required for retrospective assessment of expression. Upon completion of the dose-escalation portion of the study, the Company plans to initiate the expansion portion in combination with carboplatin for six cycles followed by UpRi monotherapy to assess feasibility as well as efficacy to inform next steps in this broader and less heavily-pretreated patient population.

NSCLC adenocarcinoma cohort of the expansion portion of Phase 1 study continues to enroll patients. The Company is on track to recruit approximately 40 patients in the expansion phase of the study. The Company plans to report interim data in the second half of 2021.
XMT-1592, first Dolasynthen ADC targeting NaPi2b:

Phase 1 dose escalation study of XMT-1592 is ongoing, with interim data anticipated in the second half of 2021. The Company has exceeded the maximum tolerated dose and continues to further explore dose and schedule. The Company plans to disclose interim data in the second half of 2021 and further outline the XMT-1592 development plan in NSCLC in the fourth quarter of 2021.
XMT-1660, first-in-class Dolasynthen ADC targeting B7-H4:

Investigational New Drug (IND)-enabling studies of XMT-1660 ongoing with Phase 1 studies expected to start in early 2022. B7-H4 is expressed in high unmet need tumors such as breast, endometrial and ovarian. B7-H4 is expressed on both tumor cells and immunosuppressive tumor-associated macrophages (TAMs). This provides the potential for both a direct, cytotoxic antitumor effect as well as for additional payload delivery to the tumor microenvironment that can further contribute to immunogenic cell death, dendritic cell activation, and stimulation of an immune response consistent with the features of the Company’s unique DolaLock payload. In a poster presented at the Virtual 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April, the Company presented preclinical data demonstrating XMT-1660’s superior efficacy compared to other potential candidate B7-H4 ADCs, covering a range of drug-to-antibody ratios, in multiple triple-negative breast cancer models as well as a ER+/HER2- breast cancer model. These data further support the clinical development of XMT-1660 for the treatment of B7-H4-expressing tumors.
XMT-2056, first Immunosynthen STING-agonist ADC:

IND-enabling studies of XMT-2056 ongoing with Phase 1 studies expected to start in early 2022. In April 2021, the Company presented two posters at AACR (Free AACR Whitepaper) highlighting preclinical efficacy of XMT-2056 as well as mechanistic data representative of the Immunosynthen platform. These data demonstrated the differentiation of XMT-2056 and its ability to induce robust anti-tumor immune activity, with only minimal increases in systemic cytokine levels, and a significant benefit over the benchmark IV-administered free STING-agonist in mice. Preclinical mechanistic data suggests that the tumor cell-intrinsic STING pathway can be activated in the presence of cues from immune cells, a potential key differentiator from other innate immune activation approaches. Further, in vitro studies showed that blocking Type III interferons (IFNs) inhibits the production of key cytokines and cancer cell killing induced by STING-agonist ADC treatment, pointing to a potentially important role for Type III IFNs in anti-tumor immune responses downstream of STING pathway activation in tumor cells. The Company plans to disclose the target for the XMT-2056 in the fourth quarter of 2021.
Corporate

Appointed Alejandra Carvajal as Senior Vice President and Chief Legal Officer. Ms. Carvajal was most recently the Chief Legal Officer, General Counsel & Secretary at Momenta Pharmaceuticals, where she led the company’s legal operations through both business restructuring and successful execution of an acquisition by Johnson & Johnson for $6.5 billion. She also served as a key strategic legal partner in the company’s financing, business development, and contractual decision-making efforts. Prior to joining Momenta, Ms. Carvajal served as the Vice President, General Counsel at Cerulean Pharma. Previously, she worked at Millennium Pharmaceuticals in several positions of increasing seniority.

Appointed Allene Diaz to Board of Directors. Ms. Diaz has over thirty years of experience in the pharmaceutical industry most recently serving as Senior Vice President of R&D portfolio management and decision sciences at GlaxoSmithKline. She previously held senior strategic product planning and commercial roles at Tesaro and Merck KGaA. She has contributed to the development, launch and commercialization of multiple global cancer therapies. Ms. Diaz is currently on the board of both BCLS Acquisition Corporation and Allena Pharmaceuticals, having previously served as a non-executive director at Erytech for three years before her current board positions.
Upcoming Events

Mersana will participate in a virtual presentation at the Jefferies Healthcare Conference scheduled for June 1-4, 2021.
A Trial in Progress poster detailing the design of the UPLIFT single-arm registration strategy evaluating UpRi in platinum resistant ovarian cancer will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting scheduled for June 4-8, 2021.
First Quarter 2021 Financial Results

Cash and cash equivalents as of March 31, 2021, were $228.4 million, compared to $255.1 million in cash and cash equivalents as of December 31, 2020. In addition, the Company has the option to draw additional funds through its debt financing agreement with Silicon Valley Bank.

Net cash used in operating activities in the first quarter of 2021 was $27.0 million. The Company expects that its available funds will be sufficient to support its operating plan commitments for approximately two years.

Research and development expenses for the first quarter of 2021 were approximately $27.4 million, compared to $12.2 million for the same period in 2020. The difference was primarily due to an increase in UpRi and XMT-1592 manufacturing, clinical and regulatory expenses, an increase in manufacturing activities for preclinical and discovery stage programs and an increase in headcount. Non-cash stock-based compensation expense included in research and development expenses increased by $1.5 million, primarily related to an increase in the valuation of stock-based awards as a result of stock appreciation.
General and administrative expenses for the first quarter of 2021 were approximately $7.2 million, compared to $4.9 million during the same period in 2020 primarily due to an increase in headcount and consulting and professional fees. Non-cash stock-based compensation expense included in general and administrative expenses increased by $0.9 million, primarily related to an increase in the valuation of stock-based awards as a result of stock appreciation.
Net loss for the first quarter of 2021 was $34.7 million, or $0.50 per share, compared to net loss of $16.9 million, or $0.35 per share, for the same period in 2020. Weighted average common shares outstanding for the quarters ended March 31, 2021 and March 31, 2020 were 68,987,857 and 47,988,630, respectively.
Conference Call Details
Mersana Therapeutics will host a conference call and webcast today at 4:30 p.m. ET to report financial results for the first quarter 2021 and provide certain business updates. To access the call, please dial 877-303-9226 (domestic) or 409-981-0870 (international) and provide the Conference ID 5046849. A live webcast of the presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com.

On May 10, 2021 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a synthetic lethality focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported financial results for the first quarter ended March 31, 2021 (Press release, Ideaya Biosciences, MAY 10, 2021, View Source [SID1234579589]).

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"We are excited to advance IDE397, a potential best-in-class MAT2A inhibitor, in the Phase 1 dose escalation for evaluation in patients with MTAP deletion tumors, including in non-small cell lung cancer (NSCLC). We are also continuing to invest in our preclinical synthetic lethality programs, including our PARG and Pol Theta programs for patients with HRD tumors, where we are targeting a development candidate for both programs in 2021," said Yujiro S. Hata, Chief Executive Officer and President of IDEAYA Biosciences.

"We are excited by the preliminary darovasertib monotherapy overall survival data in MUM and look forward to receiving FDA regulatory guidance based on the data in the second half of 2021. We are also executing on our darovasertib clinical combination strategy and are encouraged by the early partial responses observed in the combination arms, including now in the crizotinib combination. Importantly, the 54% tumor reduction by RECIST 1.1 observed in a patient treated with the darovasertib and crizotinib combination is the deepest partial response we have seen to date in the darovasertib Phase 1/2 clinical trial," said Matthew Maurer, M.D., Vice President, Head of Clinical Oncology and Medical Affairs, IDEAYA Biosciences.

Program Updates
Key highlights for IDEAYA’s pipeline programs include:
IDE397 (MAT2A)
IDEAYA is evaluating IDE397, a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2a (MAT2A), in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion, a patient population estimated to represent approximately 15% of solid tumors. IDEAYA is leading early clinical development of IDE397. Subject to exercise of its option, GlaxoSmithKline (GSK) will lead later stage global clinical development. Highlights:

Initiated a Phase 1 clinical trial designated as IDE397-001 (ClinicalTrials.gov Identifier: NCT04794699) to evaluate IDE397 under an investigational new drug application
Completed enrollment into an initial dose escalation cohort of the Phase 1 clinical trial
Clinical development plans for IDE397 include a dose escalation portion of the Phase 1 clinical trial in which IDEAYA is enrolling patients having solid tumors with MTAP gene deletion. Patients are being identified by next generation sequencing (NGS) or by MTAP immunohistochemistry (IHC) assay with confirmatory NGS
Subject to satisfactory completion of the dose escalation portion of the Phase 1 clinical trial, IDEAYA plans to enroll MTAP deletion patients into expansion arms in NSCLC and potentially in other solid tumor indications such as esophageal, gastric, bladder, head and neck, or pancreatic cancers
Planning to obtain patient biopsies from the dose escalation and expansion portions of the clinical trial for translational research, including evaluation of certain pharmacodynamic, or PD, biomarkers, such as peripheral S-adenosyl methionine (SAM), tumor SAM and tumor symmetric dimethylarginine (SDMA)
Program objective is to obtain preliminary clinical PD data from the dose-escalation portion of the IDE397 monotherapy Phase 1 clinical trial in the second half of 2021
Demonstrated preclinical efficacy of monotherapy IDE397 in a study of over forty solid tumor patient derived xenograft (PDX) models with homozygous MTAP deletions across a range of solid tumor types, including NSCLC, esophageal, gastric, bladder, head and neck, and pancreatic cancers; study data was reported at AACR (Free AACR Whitepaper) 2021 and showed:
tumor regressions, with >100% tumor growth inhibition, or TGI, in multiple PDX models across multiple solid tumor types, including in NSCLC as well as in bladder and gastric cancer models
>75% TGI in approximately 50% of models and across major solid tumor types
>60% TGI in approximately 75% of models and across major solid tumor types
dose-dependent modulation of PD biomarkers, including SDMA and SAM
Observed single-agent IDE397 preclinical activity in NSCLC PDX models, demonstrating >60% TGI in 11 independent PDX models out of 13 models evaluated in the MTAP-deletion PDX panel study, including in 7 of 9 NSCLC adenocarcinoma PDX models, and in 4 of 4 NSCLC squamous carcinoma PDX models evaluated, and demonstrating tumor regressions in 2 of 4 NSCLC squamous PDX models, including one complete response
Showed correlation of in vivo efficacy with PD modulation of tumor SDMA and tumor SAM in a study evaluating IDE397 in an MTAP-deletion NSCLC CDX model
Reported preclinical analyses of genomic and metabolic effects of pharmacological inhibition of MAT2A in an isogenic cell pair and of proliferation effects in a panel of MTAP wild type and MTAP-deleted cell lines at AACR (Free AACR Whitepaper) 2021
Observed in vivo efficacy of IDE397 in combination with a taxane, showing enhanced TGI in a pancreatic cancer PDX model, and separately in combination with a PRMT inhibitor, showing enhanced TGI in an HCT116 MTAP-null CDX model
PARG
IDEAYA is advancing preclinical research for an inhibitor of poly (ADP-ribose) glycohydrolase (PARG) in patients having tumors with a defined biomarker based on genetic mutations and/or molecular signature. PARG is a novel target in the same clinically validated biological pathway as poly (ADP-ribose) polymerase (PARP). IDEAYA owns or controls all commercial rights in its PARG program. Highlights:

Identified a novel and proprietary HRD biomarker to guide patient selection, with validation in vitro and in vivo in CDX models across multiple solid tumor indications
Demonstrated PARGi dose-dependent in vivo efficacy as monotherapy with tumor regression or stasis in ovarian, gastric and breast cancer CDX models
Observed in vivo efficacy with enhanced TGI or tumor regressions relative to niraparib, a PARPi, in multiple CDX models, including in a niraparib-resistant CDX model
Showed tumor regressions in multiple breast cancer PDX models with defined genetic and subtyping profiles
Reported preclinical data at AACR (Free AACR Whitepaper) 2021, including pharmacological inhibition of PARG in a panel of homologous recombination deficient cell lines and in CDX and PDX models
Subject to further preclinical studies, IDEAYA is targeting to identify a PARG inhibitor development candidate in 2021
Pol Theta
IDEAYA’s DNA Polymerase Theta, (Pol Theta) program targets tumors with BRCA or other homologous recombination deficiency, or HRD, mutations. IDEAYA and GSK are collaborating on ongoing preclinical research, including small molecules and protein degraders, and GSK will lead clinical development for the Pol Theta program. Highlights:

Demonstrated in vivo efficacy with tumor regression in BRCA2 -/- xenograft model with IDEAYA Pol Theta inhibitor in combination with niraparib, a GSK PARP inhibitor; and
Subject to further preclinical studies, IDEAYA is targeting selection of a Pol Theta inhibitor development candidate in 2021
Werner Helicase
IDEAYA is advancing preclinical research for an inhibitor targeting Werner Helicase for tumors with high microsatellite instability (MSI). IDEAYA and GSK are collaborating on ongoing preclinical research, and GSK will lead clinical development for the Werner Helicase program. Highlights:

observed dose-dependent cellular viability effect and dose-dependent cellular PD response in multiple endogenous MSI high cell lines
Demonstrated in vivo efficacy and PD response in relevant MSI high models
Other Synthetic Lethality Pipeline Programs
IDEAYA is advancing additional preclinical research programs to identify small molecule inhibitors for an MTAP-synthetic lethality target, as well as for multiple distinct DNA Damage Targets for patients with solid tumors characterized by a proprietary biomarker or a gene signature.

Darovasertib (IDE196)
IDEAYA continues to execute on its clinical trial strategy to evaluate darovasertib (IDE196), a potent and selective PKC inhibitor.

IDEAYA is evaluating darovasertib in metastatic uveal melanoma (MUM) as monotherapy and in combination therapies, including combinations of darovasertib / binimetinib and independently, darovasertib / crizotinib. The company is continuing to enroll MUM patients into each of these combination arms of the Phase 1/2 clinical trial, and it targeting to provide a clinical data update for the darovasertib combination(s) in the second half of 2021. Based on preliminary monotherapy clinical data in MUM and its mechanism of action, we anticipate darovasertib clinical activity independent of Human Leukocyte Antigen (HLA) status in GNAQ/11-mutation cancers.

The company is also evaluating darovasertib as monotherapy outside of MUM, with a focus in GNAQ/11-mutation skin melanoma.

Darovasertib Monotherapy
IDEAYA has completed enrollment into its ongoing Phase 1/2 clinical trial evaluating darovasertib as monotherapy in MUM patients. IDEAYA is targeting to receive FDA guidance in H2 2021 on potential regulatory path, based on the preliminary darovasertib monotherapy overall survival data in MUM. The company is continuing enrollment into its ongoing basket trial evaluating darovasertib as monotherapy in patients having non-MUM tumors harboring GNAQ or GNA11 activating mutations. The company’s development strategy in the monotherapy non-MUM GNAQ/11 arm of the clinical trial is focused on skin melanoma. Highlights:

Reported interim clinical data from Phase 1/2 clinical trial arm evaluating monotherapy darovasertib in predominantly second and third line (2L/3L) and heavily pre-treated out to seventh or eighth line (7L/8L) MUM patients. As of data and analyses cutoff on April 13, 2021 based on preliminary data from an unlocked database:
Enrolled an aggregate of 81 darovasertib monotherapy BID MUM patients across the IDEAYA and Novartis Phase 1/2 clinical trials, with 81 patients evaluable for safety and 75 patients evaluable for efficacy pursuant to RECIST 1.1 guidelines
Observed 57% 1-year overall survival (OS) with 95% confidence interval (44%, 69%), in predominantly 2L/3L and heavily pretreated to 7L/8L patients
Observed median OS of 13.2 months with 95% confidence interval (10.7 months, not reached), in predominantly 2L/3L and heavily pretreated to 7L/8L patients
Historical 37% 1-year OS and median OS of ~7 months have been reported in similar 2L/3L+ MUM patient population (Rantala 2019)
Observed tumor reduction in 61% (n=46) of 75 evaluable MUM patients pursuant to RECIST 1.1 guidelines, including 15 patients (20%) with >30% target lesion reduction, and one confirmed complete response
Reported preliminary clinical data from Phase 1/2 clinical basket trial arm evaluating monotherapy darovasertib in skin melanoma patients. As of data and analyses cutoff of April 13, 2021 based on preliminary data from an unlocked database:
Enrolled 7 darovasertib monotherapy BID skin melanoma patients in the IDEAYA Phase 1/2 clinical trial, with 7 patients evaluable for safety and 5 patients evaluable for efficacy pursuant to RECIST 1.1 guidelines
Observed tumor reduction in 80% (n=4) of 5 evaluable skin melanoma patients pursuant to RECIST1.1 guidelines, including one confirmed PR
An aggregate of 88 patients were evaluable for safety across Phase 1/2 arms evaluating darovasertib in MUM and skin melanoma patients. As of the April 13, 2021 data and analyses cutoff, and based on preliminary data from an unlocked database, the overall safety profile of darovasertib monotherapy is consistent with prior experience and includes primarily common low grade but manageable GI and skin toxicities
Preliminary clinical data from darovsertib monotherapy arm shows that darovasertib activity is independent of HLA status
Darovasertib / Binimetinib Combination Therapy
IDEAYA is continuing patient enrollment into the darovasertib / binimetinib combination arm of the Phase 1/2 clinical trial under the clinical trial collaboration and supply agreement with Pfizer. Highlights:

Initiated dose expansion evaluating the darovasertib / binimetinib combination in MUM based on early clinical activity
Amended the clinical trial collaboration and supply agreement with Pfizer to support target enrollment of approximately 40 patients in the darovasertib and binimetinib clinical combination arm
Reported preliminary clinical data from Phase 1/2 clinical trial arm evaluating the darovasertib / binimetinib combination in MUM patients, predominantly as second line, third line (2L / 3L) or later lines of treatment. As of data and analyses cutoff of April 13, 2021 based on preliminary data from an unlocked database:
24 MUM patients have enrolled in the darovasertib and binimetinib combination study and 14 of these patients were evaluable, including eight patients dosed in the Phase 1/2 dose expansion cohort of the combination study
Observed 22% (n=2) partial responses (PR), including one confirmed PR and on unconfirmed PR awaiting a confirmatory scan, of nine evaluable MUM patients with at least two post-baseline scans pursuant to RECIST 1.1 guidelines
Observed tumor reduction in 79% (n=11) of 14 evaluable MUM patients with at least one post-baseline scan pursuant to RECIST1.1 guidelines
Drug-related adverse events observed in the darovasertib and binimetinib combination arm in MUM, as of April 13, 2021 data and analyses cutoff based on preliminary data from an unlocked database, primarily include: serious adverse events of liver toxicity, nausea and vomiting, and syncope; and adverse events that occurred in greater than 10% of patients of nausea, vomiting, diarrhea, rash, edema, aminotransaminase, or AST increase, alanine aminotransferase, or ALT, increase and creatine phosphokinase increase
Darovasertib / Crizotinib Combination Therapy
IDEAYA is continuing patient enrollment into the darovasertib / crizotinib combination arm of the Phase 1/2 clinical trial under the clinical trial collaboration and supply agreement with Pfizer. Highlights:

6 MUM patients have enrolled in the darovasertib and crizotinib combination study and 2 of these patients were evaluable for response with one post-baseline scan
Observed early clinical efficacy of the darovasertib and crizotinib combination in MUM. As of data and analyses cutoff on May 5, 2021 based on preliminary data from an unlocked database, these data showed:
tumor reduction in 2 of 2 evaluable patients in a first cohort
one unconfirmed partial response in a 3rd-line patient, with a 54% tumor reduction, which is the deepest response, as reflected by the largest percentage reduction in tumor size, reported in the darovasertib clinical trial to date; this patient is awaiting a confirmatory scan
Drug-related adverse events observed in the darovasertib and crizotinib combination arm in MUM as of May 5, 2021, based on preliminary data from an unlocked database, primarily include: serious adverse events of syncope and hypotension, each of which resolved with patients continuing dosing; and adverse events that occurred in at least two of the six treated patients of nausea, diarrhea, vomiting, edema, decreased appetite, and syncope.
Initiated dose expansion for a cohort of the Phase 1/2 darovasertib / crizotinib combination arm, with additional dose exploration ongoing
Observed preclinical synergies between darovasertib and crizotinib in relevant cellular models under conditions simulating a tumor microenvironment in the liver, the site of approximately 90% of uveal melanoma metastases, as reported at AACR (Free AACR Whitepaper) 2021
Correlated cMET expression and activation to observed clinical response based on a retrospective analysis of human clinical biopsies from the Novartis darovasertib Phase 1 clinical trial, supporting cMET expression / activation as potential combination agent
General
IDEAYA continues to monitor Covid-19 and its potential impact on clinical trials and timing of clinical data results. Initiation of clinical trial sites, patient enrollment and ongoing monitoring of enrolled patients, including obtaining patient computed tomography (CT) scans, may be impacted for IDEAYA clinical trials evaluating IDE397 and darovasertib; the specific impacts are currently uncertain.

Corporate Updates
IDEAYA’s net losses were $9.0 million and $5.1 million for the three months ended March 31, 2021 and December 31, 2020, respectively. As of March 31, 2021, the company had an accumulated deficit of $136.0 million.

As of March 31, 2021, IDEAYA had cash, cash equivalents and marketable securities of $310.4 million. IDEAYA supplemented its first-quarter-end cash, cash equivalents and marketable securities with an additional $14.6 million in aggregate gross proceeds received subsequent to quarter end from the sale and issuance of common stock at a weighted average sale price of $22.99 per share under an at-the-market offering pursuant to the January 2021 Sales Agreement with Jefferies as sales agent.

IDEAYA believes that its cash, cash equivalents and marketable securities will be sufficient to fund our planned operations into 2024. These funds will support the company’s efforts through potential achievement of multiple preclinical and clinical milestones across multiple programs.

Our updated corporate presentation is available on our website, at our Investor Relations page: View Source

Financial Results
As of March 31, 2021, IDEAYA had cash, cash equivalents and short-term marketable securities totaling $310.4 million. This compared to cash, cash equivalents and short-term and long-term marketable securities of $283.6 million at December 31, 2020. The increase was primarily due to $41.8 million in net proceeds received through March 31, 2021 from issuance of common stock under at-the-market offerings pursuant to the August 2020 Sales Agreement and January 2021 Sales Agreement with Jefferies as sales agent offset by cash used in operations and purchases of property and equipment.

Collaboration revenue for the three months ended March 31, 2021 totaled $7.2 million compared to $10.6M for the three months ended December 31, 2020. Collaboration revenue was recognized for the performance obligations satisfied through March 31, 2021 under the GSK Collaboration Agreement.

Research and development (R&D) expenses for the three months ended March 31, 2021 totaled $11.6 million compared to $12.1 million for the three months ended December 31, 2020. The decrease was primarily due to a decrease in external clinical development expenses for IDE397 and darovasertib and a decrease in fees to CROs, CMOs and external consultants related to our lead product candidates, offset by an increase in R&D headcount costs.

General and administrative (G&A) expenses for the three months ended March 31, 2021 totaled $4.8 million compared to $3.8 million for the three months ended December 31, 2020. The increase was primarily due to an increase in G&A headcount costs, an increase in legal patent expense, and an increase in costs related to the filing of our shelf registration statement on Form S-3 during the quarter.

The net loss for the three months ended March 31, 2021 was $9.0 million compared to $5.1 million for the three months ended December 31, 2020. Total stock compensation expense for the three months ended March 31, 2021 was $1.9 million compared to $1.0 million for the three months ended December 31, 2020.

On May 10, 2021 Eagle Pharmaceuticals, Inc. ("Eagle" or the "Company") (NASDAQ: EGRX) reported that TREAKISYM RI (50ml) liquid formulation has been filed with the Pharmaceuticals and Medical Devices Agency ("PMDA") in Japan (Press release, Eagle Pharmaceuticals, MAY 10, 2021, View Source [SID1234579607]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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The application is based on the results of clinical studies investigating the safety and pharmacokinetics of TREAKISYM RTD administered by 10-minute intravenous infusion.

"We are pleased that the RI application has been submitted ahead of schedule, which will enable patients and providers alike to reap the benefits of this formulation. We believe we can get close to peak income of $20-$25 million as early as next year from the RTD and RI products. This is an important extension of the bendamustine franchise, and we value the relationship with Symbio," stated Scott Tarriff, Chief Executive Officer.

In September 2017, Eagle licensed to SymBio intellectual property necessary to develop, market and sell RTD and RI formulations of bendamustine under the trade name TREAKISYM in Japan utilizing Eagle’s proprietary technology. As part of the agreement, SymBio assumed responsibility for securing regulatory approval of the TREAKISYM RTD and RI products using the licensed technology in Japan.

TREAKISYM RI has the advantage of reducing infusion time to 10 minutes (from the current 60 minutes), eliminating the need for manual reconstitution and significantly reducing preparation time, benefitting both patients and healthcare providers.

On May 10, 2021 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing XCART, a personalized CAR T platform technology engineered to target patient- and tumor-specific neoantigens, reported that Jeffrey Eisenberg, Chief Executive Officer of Xenetic will present the Q2 Virtual Investor Summit on Tuesday, May 18th at 3:30 PM ET (Press release, Xenetic Biosciences, MAY 10, 2021, View Source [SID1234579635]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In addition to the presentation, management will be available to participate in virtual one-on-one meetings with qualified members of the investor community who are registered to attend the conference. For more information about the conference, please visit the conference website.

A live video webcast of the presentation will be accessible on the IR Calendar page of the Investors section of the Company’s website (xeneticbio.com) and will be archived for 90 days following the event.