On August 9, 2022 Xilio Therapeutics, Inc. (Nasdaq: XLO), a biotechnology company developing tumor-selective immuno-oncology therapies for people living with cancer, reported pipeline and business updates and reported financial results for the second quarter ended June 30, 2022 (Press release, Xilio Therapeutics, AUG 9, 2022, View Source [SID1234617900]).

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"We are encouraged by the preliminary dose-escalation data reported today for XTX101, a tumor-selective anti-CTLA-4. These data provide initial clinical validation of Xilio’s geographically precise solutions (GPS) platform and demonstrate that XTX101 has reached dose levels above the target dose with limited active (unmasked) molecule in peripheral circulation. Based on these data, we plan to explore a Phase 2 clinical trial for XTX101 in microsatellite stable (MSS) colorectal cancer," said René Russo, Pharm.D., chief executive officer of Xilio. "With a strong balance sheet and experienced leadership team, we are well-positioned to continue to advance our pipeline and anticipate multiple clinical data milestones for XTX101 and XTX202 in 2023."

XTX101: Preliminary Dose-Escalation Data from Ongoing Phase 1 Clinical Trial

XTX101, an Fc-enhanced, tumor-selective anti-CTLA-4, is being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors. The target dose level for XTX101 of 60 mg is anticipated to provide anti-tumor activity similar to ipilimumab at 10 mg/kg (approximately 600 mg in a 60 kg patient) based on the 10 times greater potency observed for XTX101 relative to an ipilimumab analogue in preclinical studies.

As of August 5, 2022, 12 patients have been treated with XTX101 in the monotherapy dose-escalation cohort (Part 1A) at four dose levels ranging from 7 mg to 180 mg:

The 180 mg dose level has surpassed the 60 mg target dose level for XTX101. As a result, Xilio recently expanded enrollment at the 180 mg dose level.
A maximum tolerated dose (MTD) has not yet been determined, and enrollment in the dose-escalation cohort is ongoing.
Preliminary pharmacokinetic (PK) analyses demonstrated dose-proportional drug exposure, with limited active (unmasked) XTX101 in peripheral circulation (range of % active in periphery: 6% – 16%) consistent with PK data observed in preclinical studies.
Additional XTX101 Development Updates

Xilio recently opened Part 1B of the clinical trial for patient enrollment, which is a monotherapy cohort designed to evaluate anti-tumor activity, including intra-tumoral PK and pharmacodynamic (PD) data, in patients with anti-CTLA-4 sensitive tumor types, with the goal of characterizing the anti-tumor activity of XTX101 at one or more dose levels selected in Part 1A of the trial.
Given the potential for Fc-enhanced anti-CTLA-4 agents like XTX101 to demonstrate activity in tumors that are historically resistant to immuno-oncology treatment, Xilio plans to explore evaluating XTX101 in a Phase 2 clinical trial in patients with microsatellite stable (MSS) colorectal cancer in combination with an anti-PD(L)-1.
XTX202: Phase 1 Clinical Trial Progress

XTX202, a tumor-selective, engineered IL-2, is being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors. As of August 5, 2022, six patients have been treated with XTX202 as outpatients in the monotherapy dose-escalation cohort (Part 1A) at three dose levels ranging from 0.27 mg/kg to 0.53 mg/kg. An MTD has not yet been determined, and enrollment in the dose-escalation cohort is ongoing.

Upcoming Anticipated Milestones

Xilio anticipates multiple milestones through the end of 2023:

XTX101

Report data from Part 1A of the trial (monotherapy dose-escalation cohort) supporting the recommended Phase 2 dose (RP2D) in the first half of 2023. Xilio anticipates the data for Part 1A will include available safety and anti-tumor activity, as well as peripheral PK and PD data.
Report preliminary data from Part 1B of the trial (monotherapy expansion cohort) in the middle of 2023. Xilio anticipates the data for Part 1B will include available safety and anti-tumor activity, as well as intra-tumoral PK and PD data.
Initiate patient enrollment in Part 1C of the trial (pembrolizumab combination cohort) in the fourth quarter of 2022.
Report preliminary data from Part 1C of the trial in the first half of 2023. Xilio anticipates the data will include available safety and anti-tumor activity, as well as peripheral PK and PD data for XTX101 in combination with pembrolizumab.
XTX202

Report data from Part 1A of the trial (monotherapy dose-escalation cohort) supporting the RP2D in the first half of 2023. Xilio anticipates the data will include available safety and anti-tumor activity, as well as peripheral PK and PD data.
Initiate patient enrollment in Part 1B (monotherapy expansion cohort) in the fourth quarter of 2022. Part 1B is a monotherapy cohort designed to evaluate anti-tumor activity of XTX202 in a basket of indications potentially sensitive to IL-2.
Report preliminary data from Part 1B of the trial (monotherapy expansion cohort) in the second half of 2023. Xilio anticipates the data will include available safety and anti-tumor activity data.
Following the determination of a RP2D, Xilio anticipates initiating a Phase 2 monotherapy trial in the first half of 2023 designed to evaluate the safety and efficacy of XTX202 in patients with melanoma and renal cell carcinoma (RCC). Xilio anticipates enrolling a total of approximately 35 patients across both cohorts in the Phase 2 clinical trial.
XTX301

Submit an investigational new drug application (IND) to the U.S. Food and Drug Administration (FDA) for XTX301 in the fourth quarter of 2022.
Subject to FDA clearance of the IND, Xilio plans to initiate a Phase 1 clinical trial in the first half of 2023 evaluating the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors. The Phase 1 clinical trial will consist of a monotherapy dose-escalation cohort with the goal of determining a RP2D for XTX301 and monotherapy expansion cohorts at the RP2D.
Corporate Highlights

Today, Xilio announced the promotions of Uli Bialucha, Ph.D., to chief scientific officer and Chris Frankenfield to chief legal and administrative officer, each effective as of August 8, 2022. Dr. Bialucha previously served as the company’s senior vice president of research since April 2021, and Mr. Frankenfield previously served as the company’s general counsel since March 2021.
In June 2022, Xilio announced the promotion of Martin Huber, M.D., to president, the election of Paul Clancy as chair of the board of directors, and the appointment of Robert Ross, M.D., as a member of the board of directors.
In May 2022, Xilio announced the appointment of Stacey Davis as chief business officer.
Second Quarter 2022 Financial Results

Cash Position: Cash and cash equivalents were $159.4 million as of June 30, 2022, compared to $198.1 million as of December 31, 2021.
Research & Development (R&D) Expenses: R&D expenses were $16.2 million for the second quarter of 2022, compared to $17.7 million for the second quarter of 2021. The decrease was primarily driven by decreased costs associated with XTX202 manufacturing and preclinical activities, partially offset by increased costs associated with XTX301, as well as higher personnel-related costs mainly due to increased headcount, including a $0.3 million increase in non-cash equity-based compensation expense.
General & Administrative (G&A) Expenses: G&A expenses were $8.3 million for the second quarter of 2022, compared to $5.3 million for the second quarter of 2021. The increase was primarily driven by higher personnel-related costs, primarily due to increased headcount and a $1.4 million increase in non-cash equity-based compensation expense, as well as certain costs related to operating as a publicly traded company.
Net Loss: Net loss was $24.6 million for the second quarter of 2022, compared to $23.2 million for the second quarter of 2021.
Financial Guidance

Xilio continues to anticipate that its existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into the first half of 2024.

About the Phase 1 Clinical Trial for XTX101

XTX101 is an investigational Fc-enhanced, tumor-selective anti-CTLA-4 monoclonal antibody designed to deplete regulatory T cells when activated selectively (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 as a monotherapy, as well as a combination therapy with pembrolizumab, for the treatment of adult patients with advanced solid tumors. The Phase 1 portion of the trial consists of three cohorts. The first cohort (Part 1A) is an accelerated and standard 3+3 dose-escalation monotherapy cohort designed to assess the tolerability of XTX101 in patients with advanced solid tumors who have progressed after receiving the standard-of-care treatment for their tumor. The second cohort (Part 1B) is a monotherapy cohort designed to evaluate evidence of anti-CTLA-4 pharmacodynamic activity in patients who have progressed on anti-PD-1 or anti-PD-L1 treatment but have not received prior treatment with an anti-CTLA-4 therapy. The third cohort (Part 1C) is a combination therapy cohort designed to evaluate XTX101 in combination with pembrolizumab in patients who have not previously been treated with an anti-PD-1 or anti-PD-L1 treatment. The Phase 1 clinical trial is designed to enroll a total of up to approximately 104 patients across all cohorts at multiple sites in the United States. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

In May 2021, Xilio entered into a clinical trial collaboration and supply agreement with Merck & Co., Inc. (known as MSD outside the US and Canada) to explore the therapeutic potential of XTX101 in combination with pembrolizumab in patients with advanced solid tumors.

About the Phase 1 Clinical Trial for XTX202

XTX202 is an investigational tumor-selective beta-gamma biased (non-alpha), engineered IL-2 molecule designed to potently stimulate CD8 and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated selectively (unmasked) in the TME. The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX202 as a monotherapy in patients with advanced solid tumors. The Phase 1 clinical trial is designed to enroll a total of up to approximately 48 patients across all cohorts at multiple sites in the United States. Please refer to NCT05052268 on www.clinicaltrials.gov for additional details.

About XTX301

XTX301 is an investigational tumor-selective, engineered IL-12 designed to potently stimulate anti-tumor immunity and reprogram the TME of poorly immunogenic "cold" tumors towards an inflamed, or "hot," state. IL-12 plays a key role in bridging innate and adaptive cellular immunity, making it a compelling target for immunotherapy. However, dose-limiting toxicities observed with systemically active IL-12, including life-threatening liver toxicity, have limited the therapeutic potential of IL-12 agents to date. Preclinical studies using a murine surrogate molecule for XTX301 demonstrated in vivo anti-tumor activity at doses as low as 0.04 mg/kg and favorable tolerability. Xilio has completed GLP toxicology studies for XTX301.

On August 9, 2022 Exelixis, Inc. (Nasdaq: EXEL) reported financial results for the second quarter of 2022 and provided an update on progress toward achieving key corporate objectives, as well as commercial, clinical and pipeline development milestones (Press release, Exelixis, AUG 9, 2022, View Source [SID1234617916]).

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"In the second quarter of 2022, Exelixis continued to execute across each of the core components of our business, highlighted in particular by our commercial and pipeline activities," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer, Exelixis. "The team drove strong commercial performance for CABOMETYX (cabozantinib), resulting in a 22 percent growth in cabozantinib franchise net product revenues year-over-year. In addition, we achieved key cabozantinib milestones, including generating positive data for the progression-free survival primary endpoint of our COSMIC-313 clinical trial and supporting Ipsen as it successfully pursued its CABOMETYX label expansion for a differentiated thyroid cancer indication in the European Union and Canada."

Dr. Morrissey continued: "Exelixis also made significant pipeline advancements during and after the close of the quarter, initiating STELLAR-303, our first phase 3 pivotal study for XL092, as well as the first-in-human phase 1 study for XL114 in non-Hodgkin’s lymphoma. Additionally, we signed new business development agreements with BioInvent and Ryvu Therapeutics to further expand our biologics capabilities and portfolio of biotherapeutics candidates. Moving into the second half of this year, we have much to look forward to, including the potential to further augment the CABOMETYX label through upcoming clinical data readouts expected from the CONTACT-01 and CONTACT-03 pivotal studies in non-small cell lung cancer and renal cell carcinoma, respectively, as well as anticipated clinical updates from our XL092, XB002 and XL102 pipeline programs. I want to thank the Exelixis team for their continued hard work and dedication during the second quarter as we continue to advance our mission on behalf of the patients we serve."

Second Quarter 2022 Financial Results

Total revenues for the quarter ended June 30, 2022 were $419.4 million, compared to $385.2 million for the comparable period in 2021.

Total revenues for the quarter ended June 30, 2022 included net product revenues of $347.0 million, compared to $284.2 million for the comparable period in 2021. The increase in net product revenues was primarily due to an increase in sales volume, which was partially offset by increases in discounts and allowances, primarily from higher utilization in the 340B Drug Pricing Program.

Collaboration revenues, composed of license revenues and collaboration services revenues, were $72.4 million for the quarter ended June 30, 2022, compared to $100.9 million for the comparable period in 2021. The decrease in collaboration revenues was primarily related to a decrease in development cost reimbursements earned, which was partially offset by an increase in the recognition of milestone-related revenues, and higher royalty revenues for the sales of cabozantinib outside of the U.S. generated by Exelixis’ collaboration partners, Ipsen Pharma SAS (Ipsen) and Takeda Pharmaceutical Company Limited (Takeda).

Research and development expenses for the quarter ended June 30, 2022 were $199.5 million, compared to $148.8 million for the comparable period in 2021. The increases in research and development expenses were primarily related to increases in personnel expenses, clinical trial costs, license and other collaboration costs, and consulting and outside services expenses, which were partially offset by a decrease in stock-based compensation expense.

Selling, general and administrative expenses for the quarter ended June 30, 2022 were $122.8 million, compared to $98.5 million for the comparable period in 2021. The increases in selling, general and administrative expenses were primarily related to increases in personnel expenses, marketing costs, business technology initiatives and legal costs.

Provision for income taxes for the quarter ended June 30, 2022 was $17.8 million, compared to $28.8 million for the comparable period in 2021, primarily due to a decrease in pre-tax income.

GAAP net income for the quarter ended June 30, 2022 was $70.7 million, or $0.22 per share, basic and diluted, compared to GAAP net income of $96.1 million, or $0.31 per share, basic and $0.30 per share, diluted, for the comparable period in 2021.

Non-GAAP net income for the quarter ended June 30, 2022 was $89.7 million, or $0.28 per share, basic and diluted, compared to non-GAAP net income of $117.9 million, or $0.38 per share, basic and $0.37 per share, diluted, for the comparable period in 2021.

Cash, cash equivalents, restricted cash equivalents and investments were $2.0 billion at June 30, 2022, compared to $1.9 billion at December 31, 2021.

Non-GAAP Financial Measures

To supplement Exelixis’ financial results presented in accordance with U.S. Generally Accepted Accounting Principles (GAAP), Exelixis presents non-GAAP net income (and the related per share measures), which excludes from GAAP net income (and the related per share measures) stock-based compensation expense, adjusted for the related income tax effect for all periods presented.

Exelixis believes that the presentation of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors. In particular, Exelixis believes that these non-GAAP financial measures, when considered together with its financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare Exelixis’ results from period to period, and to identify operating trends in Exelixis’ business. Exelixis has excluded stock-based compensation expense, adjusted for the related income tax effect, because it is a non-cash item that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. Exelixis also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate its business and to make operating decisions.

These non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. Exelixis encourages investors to carefully consider its results under GAAP, as well as its supplemental non-GAAP financial information and the reconciliation between these presentations, to more fully understand Exelixis’ business. Reconciliations between GAAP and non-GAAP results are presented in the tables of this release.

2022 Financial Guidance

(1) Includes $45 million of non-cash stock-based compensation expense.
(2) Includes $50 million of non-cash stock-based compensation expense.

Cabozantinib Highlights

Cabozantinib Franchise Net Product Revenues and Royalties. Net product revenues generated by the cabozantinib franchise in the U.S. were $347.0 million during the second quarter of 2022, up 12% over the prior quarter, comprised of net product revenues of $339.2 million from CABOMETYX and $7.9 million from COMETRIQ (cabozantinib). In the second quarter of 2022, global cabozantinib franchise net product revenues generated by Exelixis and its partners were almost $500 million. Exelixis earned $30.2 million in royalty revenues during the quarter ended June 30, 2022, pursuant to collaboration agreements with its partners, Ipsen and Takeda.

Exelixis’ Partner Ipsen Receives European Commission (EC) and Health Canada Approvals for CABOMETYX for Patients with Previously Treated Radioactive Iodine (RAI)-Refractory Differentiated Thyroid Cancer (DTC). In May, Exelixis announced its partner Ipsen received approval from the EC for CABOMETYX as a monotherapy for the treatment of adult patients with locally advanced or metastatic DTC, refractory or not eligible to RAI who have progressed during or after prior systemic therapy. This approval allows for the marketing of CABOMETYX in this indication in all 27 member states of the European Union, Norway, Liechtenstein and Iceland. Similarly, in late April 2022, Ipsen received approval from Health Canada to market CABOMETYX for a similar DTC indication in Canada. As a result of these approvals, Exelixis was eligible to receive $27.0 million in milestone payments from Ipsen, of which $25.7 million was recognized in license revenues and collaboration services revenues in the second quarter of 2022. Both approvals were based on the positive results of the phase 3 COSMIC-311 pivotal trial.

Cabozantinib Data Presentations at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. In June, cabozantinib was the subject of 13 presentations at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting, held from June 3-7 in Chicago. Notable presentations included results from: cohorts 7 and 20 in non-small cell lung cancer; cohorts 3, 4 and 5 in urothelial carcinoma from the ongoing COSMIC-021 study evaluating cabozantinib in combination with atezolizumab across multiple tumor types; and a phase 2 investigator-sponsored trial from the Emory Winship Cancer Institute evaluating the combination of cabozantinib and pembrolizumab in recurrent metastatic head and neck squamous cell carcinoma.

Announcement of Top-line Results from the COSMIC-313 Phase 3 Pivotal Trial Evaluating Cabozantinib in Combination with Nivolumab and Ipilimumab in Previously Untreated Advanced Renal Cell Carcinoma (RCC). In July, Exelixis announced that COSMIC-313 met its primary endpoint, demonstrating significant improvement in progression-free survival (PFS) at the primary analysis. At a prespecified interim analysis for the secondary endpoint of overall survival (OS), the combination of cabozantinib, nivolumab and ipilimumab versus the combination of nivolumab and ipilimumab did not demonstrate a significant benefit. Therefore, the trial will continue to the next analysis of OS. COSMIC-313 is an ongoing phase 3 pivotal trial evaluating the combination of cabozantinib, nivolumab and ipilimumab versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk RCC. Exelixis intends to discuss the results with the U.S. Food & Drug Administration (FDA) to determine next steps toward a potential regulatory submission for the combination regimen for patients with previously untreated advanced intermediate- or poor-risk RCC. Detailed findings will be presented at a future medical meeting.

Pipeline Highlights

Initiation of First-In-Human Phase 1 Trial Evaluating XL114 Monotherapy in Patients with Non-Hodgkin’s Lymphoma (NHL). In April, Exelixis announced the initiation of the dose-escalation stage of the first-in-human phase 1 trial of XL114, a novel anti-cancer compound that inhibits the CARD11-BCL10-MALT1 complex, as a monotherapy in patients with NHL who have received prior standard therapies. The objectives of the study are to determine the recommended dose and/or the maximum tolerated dose of XL114 and to evaluate the safety and preliminary efficacy of XL114 in patients with NHL. The dose-escalation stage will determine the recommended dose of XL114 in patients with advanced B- and T-cell NHL. In the cohort-expansion stage, the safety and preliminary efficacy of XL114 will be further evaluated in various B-cell NHL-specific expansion cohorts. The primary endpoint of the expansion stage will be objective response rate (ORR) based on lymphoma-specific response criteria as assessed by the investigator.

Initiation of the STELLAR-303 Phase 3 Pivotal Trial Evaluating XL092 in Patients with Metastatic Colorectal Cancer (CRC). In June, Exelixis announced the initiation of STELLAR-303, a phase 3 pivotal trial evaluating XL092 in combination with atezolizumab versus regorafenib in patients with metastatic CRC that is not microsatellite instability-high or mismatch repair-deficient, who have progressed after or are intolerant to the standard of care therapy. STELLAR-303 is a global, multicenter, randomized phase 3 open-label study that will enroll approximately 600 patients with documented RAS status. The primary objective of the study is to evaluate the efficacy of the combination in patients with RAS wild-type disease, and outcomes in patients with RAS-mutated disease will also be evaluated. The primary endpoint is OS, and secondary endpoints include PFS, ORR and duration of response per Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by the investigator. XL092 is Exelixis’ next-generation tyrosine kinase inhibitor in development for multiple advanced tumor types.

Corporate Updates

Exclusive Option and License Agreement with BioInvent International AB (BioInvent) to Develop Novel Antibody-Based Oncology Therapies. In June, Exelixis and BioInvent entered into an option and license agreement focused on the identification and development of novel antibodies for use as oncology therapeutics. The collaboration is intended to expand Exelixis’ portfolio of antibody-based therapies. Target and antibody discovery will be performed using BioInvent’s proprietary n-CoDeR antibody library and patient-centric F.I.R.S.T screening platform, which together allow for parallel target and antibody discovery. Under the terms of the agreement, Exelixis paid BioInvent an upfront fee of $25.0 million in exchange for rights to select three targets identified using BioInvent’s proprietary F.I.R.S.T platform and n-CoDeR library, and will have the right to exercise an option to in-license any of the target programs upon identification of a development candidate directed to that target. Upon option exercise, Exelixis will assume responsibility for all future development and commercialization activities for the development candidate, including potential antibody-drug conjugate (ADC) and bispecific antibody engineering activities.

Exclusive License Agreement with Ryvu Therapeutics S.A. (Ryvu) to Develop Novel STING Agonist-Based Targeted Cancer Therapies. In July, Exelixis and Ryvu announced an exclusive license agreement focused on the development of novel targeted therapies utilizing Ryvu’s STING (STimulator of INterferon Genes) technology. The collaboration is intended to expand Exelixis’ portfolio of biotherapeutics by combining its tumor-specific targeting approaches with Ryvu’s proprietary small molecule STING agonists and STING biology know-how. Under the terms of the agreement, Exelixis is obligated to pay Ryvu an upfront fee of $3.0 million in exchange for certain rights to Ryvu’s STING agonist small molecules, which Exelixis will seek to incorporate into targeted therapies such as ADCs. Exelixis will lead all research activities and, upon selection of each development candidate, will be responsible for all development and commercialization activities. Ryvu will provide expert guidance and know-how during the early research phase of the partnership.

Basis of Presentation

Exelixis has adopted a 52- or 53-week fiscal year that generally ends on the Friday closest to December 31st. For convenience, references in this press release as of and for the fiscal periods ended July 1, 2022, and July 2, 2021, are indicated as being as of and for the periods ended June 30, 2022, and June 30, 2021, respectively.

Conference Call and Webcast

Exelixis management will discuss the company’s financial results for the second quarter of 2022 and provide a general business update during a conference call beginning at 5:00 p.m. ET / 2:00 p.m. PT today, Tuesday, August 9, 2022.

To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, please call 888-338-9509 (domestic) or 412-902-4281 (international) and ask to be joined into the Exelixis conference call to participate by phone.

A telephone replay will be available until 8:00 p.m. ET on Thursday, August 11, 2022. Access numbers for the telephone replay are: 877-344-7529 (domestic) and 412-317-0088 (international); the passcode is 8698613. A webcast replay will also be archived on www.exelixis.com for one year.

On August 9, 2022 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology," Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers, reported second quarter financial results for the period ended June 30, 2022, and provided a business update (Press release, Olema Oncology, AUG 9, 2022, View Source [SID1234617932]).

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"Our objective is for OP-1250 to become the endocrine therapy of choice for ER+ breast cancer and, based on the progress we are making across the program and receipt of Fast Track designation from FDA, we believe we are well on our way toward achieving that goal. Our enrollment continues to be robust and the emerging data show a favorable tolerability profile, encouraging early anti-tumor activity, and combinability with palbociclib," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "As we continue to generate more data, OP-1250 is revealing its potential, validating our confidence to move ahead our next set of trials and preparing for a pivotal monotherapy study next year. We are well capitalized into the second half of 2024, and we look forward to presenting more data as the year progresses."

Recent Corporate Highlights

Received Fast Track designation from the U.S. Food and Drug Administration (FDA) for OP-1250 for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. A drug candidate that receives Fast Track designation is eligible for more frequent communication with the FDA throughout the drug development process for the purpose of expediting the drug’s development, review and potential approval.
Announced interim data from Phase 1b monotherapy expansion of OP-1250 for ER+/HER2- breast cancer.
Based on pharmacokinetics, safety and tolerability, and encouraging early anti-tumor activity in Phase 1b monotherapy expansion, 120 mg once-daily dosing of OP-1250 was selected as the recommended Phase 2 dose (RP2D).
Following the selection of RP2D, Phase 2 enrollment continues and will include three cohorts: patients with measurable disease (N=50), patients with non-measurable disease (N=15) and patients with CNS metastasis (N=15).
Dose escalation in the Phase 1b combination study with the CDK4/6 inhibitor palbociclib continues, with evaluation at 120 mg OP-1250 ongoing. Combinability has been demonstrated across the completed dose escalation cohorts (30 mg, 60 mg and 90 mg OP-1250), including no dose limiting toxicities, no induced metabolism of palbociclib, and overall tolerability consistent with expected profile of palbociclib plus an endocrine therapy.
Announced an exclusive global license agreement with Aurigene Discovery Technologies Limited (Aurigene) to research, develop and commercialize novel small molecule inhibitors of an undisclosed oncology target.
Anticipated Milestones

Initiate a Phase 1b combination study with each of ribociclib, a CDK4/6 inhibitor, and alpelisib, a PI3Kɑ inhibitor, in the third quarter of 2022.
Present updated monotherapy and initial combination data with palbociclib at medical meetings in the fourth quarter of 2022, pending abstract acceptance.
Initiate a pivotal monotherapy study in second-line or later settings in mid-2023.
Present additional monotherapy and combination data in 2023.
Financial Results

Cash, cash equivalents and marketable securities as of June 30, 2022, were $240.7 million. Olema anticipates that this balance will be sufficient to fund operations into the second half of 2024.
Net loss for the quarter ended June 30, 2022, was $32.9 million, compared to $16.4 million for the same period of the prior year. The increase in net loss related primarily to Olema’s continued investment in OP-1250, increased spending on research and development activities, including the $8.0 million upfront payment to Aurigene, and an increase in general and administrative (G&A) costs.
GAAP research and development (R&D) expenses were $27.1 million for the quarter ended June 30, 2022, compared to $11.9 million for the same period of the prior year. The increase in R&D expenses was primarily related to the advancement of the development program for OP-1250 and an increase in nonclinical research and discovery program activities, including the $8.0 million upfront payment to Aurigene. Non-GAAP R&D expenses were $23.9 million for the quarter ended June 30, 2022, excluding $3.2 million of non-cash stock-based compensation expense. Non-GAAP R&D expenses were $9.6 million for the quarter ended June 30, 2021, excluding $2.3 million of non-cash stock-based compensation expense. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this news release.
GAAP G&A expenses were $6.2 million for the quarter ended June 30, 2022, as compared to $4.6 million for the same period of the prior year. The increase in G&A expenses was primarily related to higher personnel-related expenses and other corporate costs. Non-GAAP G&A expenses were $4.7 million for the quarter ended June 30, 2022, excluding $1.5 million of non-cash stock-based compensation expense. Non-GAAP G&A expenses were $3.0 million for the quarter ended June 30, 2021, excluding $1.6 million of non-cash stock-based compensation expense.

On August 9, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported results from preclinical in vitro studies for its highly selective CDK9 inhibitor, GFH009, in solid cancer and acute myeloid leukemia (AML) cell lines (Press release, Sellas Life Sciences, AUG 9, 2022, View Source [SID1234617948]). The data shows that GFH009 demonstrated significant anti-tumor effects in all four selected cell lines. In three out of the four cell lines, GFH009 inhibited cancer cell growth by 90 to 100 percent.

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The in vitro studies were conducted at an independent, third-party contract research organization, Translational Drug Development (TD2), and the following cell lines were selected for the studies based on their unique characteristics, combined with GFH009’s mechanism of action:

RH30: a pediatric soft tissue sarcoma cell line that is a model for studying high-risk pediatric rhabdomyosarcoma, an indication for which currently available treatments are limited to high-dose chemotherapy with unsatisfactory results. RH30 cells are driven by PAX3-FOXO1, a transcription factor whose expression is strictly needed for tumor cell survival. RH30 is also dependent on MYCN, a major target of CDK9 inhibition. Treatment with GFH009 resulted in 90 percent or more cancer inhibition at dose levels equivalent to those already demonstrated to be safe in patients in the ongoing Phase 1 trial with no viable cancer cells at the highest dose levels.

NCI-H209: a small cell lung cancer cell line characterized by the loss of function of two major tumor suppressor genes, RB1 and TP53. This cell line also expresses MCL-1, a major target of CDK9 inhibition. Treatment with GFH009 resulted in 90 percent or more cancer inhibition at dose levels equivalent to those already demonstrated to be safe in patients in the ongoing Phase 1 trial with no viable cancer cells at highest dose levels.

SKOV-3: an ovarian cancer cell line containing the wild type BRCA1 gene and highly expresses CDK9. Treatment with GFH009 resulted in more than 50 percent cancer inhibition at dose levels equivalent to those already demonstrated to be safe in patients in the ongoing Phase 1 trial.

OCI-AML-2: an AML cell line that develops resistance to the chemotherapy venetoclax on exposure. Treatment with GFH009 resulted in 90 to 100 percent cancer inhibition at dose levels equivalent to those already demonstrated to be safe in patients in the ongoing Phase 1 trial with no viable cancer cells at the highest dose levels.
"The data from preclinical studies that we are reporting today demonstrates that certain cancer cell lines, whose survival depends on specific changes in the cell, can be identified and treated with GFH009," said Dragan Cicic, MD, Senior Vice President, Clinical Development, of SELLAS. "Through identifying specific genes in cancer cells, GFH009 has shown in these preclinical studies the ability to stop the transcription and expression from gene to protein, inhibiting cancer cell growth altogether. We will utilize this important information as we design our clinical development program for GFH009 in adult and pediatric tumor types."

About Translational Drug Development (TD2)
TD2 is an oncology development organization that provides innovative services for oncology-focused companies. Using a dedicated team of professionals with broad experience and understanding in drug development, TD2 is uniquely positioned to support improved and accelerated development of medicines for life-threatening oncology diseases. TD2 applies rigorous and high-throughput translational preclinical development, combined with regulatory affairs expertise, to customize clinical trial design and execution. TD2’s suite of capabilities encourages the timely selection of patient populations who are most likely to benefit from a new agent, and the rapid identification of clinically significant endpoints. TD2 is committed to reducing the risks and uncertainty inherent in the drug development process and to the acceleration of patient access to promising treatments. For more information, visit www.TD2inc.com.

On August 9, 2022 BioMarker Strategies reported that the journal CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS has published a manuscript by the Company’s scientists entitled "Functional Profiling of Head and Neck/Esophageal Squamous Cell Carcinoma to Predict Cetuximab Response" (Press release, BioMarker Strategies, AUG 9, 2022, View Source [SID1234617963]). The manuscript describes the company’s progress in identifying predictive dynamic biomarkers to help identify the subset of patients with head and neck/esophageal squamous cell carcinoma (SCC) who may benefit from treatment with cetuximab (Erbitux) and biosimilars.

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Cetuximab is an antibody that targets an epidermal growth factor receptor (EGFR), and remains the only targeted therapy approved by the U.S. Food and Drug Administration (FDA) for SCC of head and neck/esophagus. For primary SCC, cetuximab is approved for use in combination with radiation. In metastatic SCC, it is approved for use in combination with platinum chemotherapy and fluorouracil.

The authors note that responses to cetuximab can be dramatic, but the response rate was only about 15% in the landmark clinical trial. The authors also note that cetuximab therapy is accompanied by a risk of serious adverse events that results in interrupted therapy in 3%-10% of patients. The cost of treatment is approximately $100,000 per patient. Additionally, immune checkpoint inhibitors are now an option in SCC. Therefore, methods to identify patients who are most likely to respond to cetuximab are needed.

SCC is the world’s sixth most common cancer. Worldwide, there are approximately 900,000 new cases and 450,000 deaths per year. In the United States alone there are approximately 66,630 new cases and 14,620 deaths per year.

"To minimize risk and maximize the therapeutic benefit of cetuximab, predictive tests to better identify patients likely to be responsive to cetuximab therapy are clearly an important need," said Jerry Parrott, President and CEO of BioMarker Strategies. "From my perspective, based on the results reported here, I would agree with the authors that further studies are warranted to test in more complex samples, including patient-derived tumor tissues."

The research described in the manuscript discussed here was supported by a Small Business Innovation Research (SBIR) award from the National Cancer Institute (NCI) of the National Institutes of Health (NIH).