On March 2, 2023 AstraZeneca and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) will convene a meeting of the Oncologic Drugs Advisory Committee (ODAC) to discuss the supplemental new drug application (sNDA) for use of LYNPARZA in combination with abiraterone and prednisone or prednisolone (abi/pred) for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Merck & Co, MAR 2, 2023, View Source [SID1234628082]). The ODAC provides the FDA with independent, expert advice and recommendations on marketed and investigational medicines for use in the treatment of cancer. The FDA is not bound by the committee’s guidance but takes its advice into consideration.

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The ODAC Meeting is scheduled for April 28, 2023. AstraZeneca and Merck are committed to working with the FDA to bring LYNPARZA in combination with abi/pred to patients diagnosed with mCRPC.

The sNDA is based on the results of the Phase 3 PROpel trial. Results from PROpel, including the primary endpoint of radiographic progression-free survival (rPFS), were first presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers (GU) Symposium and subsequently published in NEJM Evidence. Results from the final pre-specified overall survival (OS) analysis were presented at ASCO (Free ASCO Whitepaper) GU 2023.

LYNPARZA in combination with abi/pred is approved in the European Union and several other countries for the treatment of adult patients with mCRPC, based on the PROpel trial.

About PROpel

PROpel is a randomized, double-blind Phase 3 trial testing the efficacy, safety and tolerability of LYNPARZA versus placebo when given in addition to abi/pred in patients with mCRPC who had not received prior chemotherapy or new hormonal agents in the mCRPC setting. The major efficacy outcome was rPFS as assessed by investigator per RECIST v1.1 and Prostate Cancer Working Group (bone) criteria. OS was an additional efficacy outcome measure.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in 0.8% of patients exposed to LYNPARZA monotherapy, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Venous Thromboembolic Events (VTE): Including severe or fatal pulmonary embolism (PE) occurred in patients treated with LYNPARZA. VTE occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Males

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab

Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab and at a ≥5% frequency compared to placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%), and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%).

In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%), and decrease in platelets (35%).

ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%), and dyspepsia (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%).

ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in >25% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab

In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either:

a deleterious or suspected deleterious BRCA mutation, and/or
genomic instability
Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer

For the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm, HER2-Negative Metastatic Breast Cancer

For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please see complete Prescribing Information, including Medication Guide.

About LYNPARZA (olaparib)

LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR.

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.

About metastatic castration-resistant prostate cancer

Prostate cancer is the second most common cancer in male patients globally and is associated with a significant mortality rate. Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body, despite the use of androgen-deprivation therapy to block the action of male sex hormones. Approximately 10-20% of patients with prostate cancer are estimated to develop castration-resistant prostate cancer (CRPC) within five years, with at least 84% of these patients presenting with metastases at the time of CRPC diagnosis. Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.

About the AstraZeneca and Merck strategic oncology collaboration

In July 2017, AstraZeneca and Merck, known as MSD outside of the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products including LYNPARZA, the world’s first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines.

Merck’s focus on cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On March 2, 2023 GlycoMimetics presenting its corporate presentation (Presentation, GlycoMimetics, MAR 2, 2023, View Source [SID1234628080]).

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On March 2, 2023 Cardinal Health, Inc. (the "Company"), JPMorgan Chase Bank, N.A., as Administrative Agent, Joint Lead Arranger and Joint Book Manager, Bank of America, N.A. and Wells Fargo Bank, National Association as Syndication Agents, Barclays Bank PLC, Deutsche Bank Securities, Inc., Goldman Sachs Bank USA, HSBC Bank USA, N.A., and MUFG Bank, Ltd. as Documentation Agents, and BofA Securities, Inc. and Wells Fargo Securities, LLC, as Joint Lead Arrangers and Joint Book Managers, reported that it has entered into a Third Amended and Restated Five-Year Credit Agreement (the "Credit Agreement") (Filing, 8-K, Cardinal Health, MAR 2, 2023, View Source [SID1234628079]).

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The Credit Agreement, among other things, allows the Company access to $2.0 billion of revolving credit and extends the term of the Company’s revolving credit facility to February 25, 2028. The expiration date of the Credit Agreement may be extended for up to two additional one year periods, subject to certain restrictions (including the consent of the lenders). Interest rates on borrowings under the Credit Agreement will be based on prevailing interest rates, benchmarked based on Term SOFR and subject to the Company’s credit ratings, as described in the Credit Agreement.

The Credit Agreement contains customary representations and affirmative and negative covenants (including restrictions on incurring liens, subsidiary indebtedness and contingent obligations). The financial covenants in the Credit Agreement require the Company to maintain, as of the last day of any fiscal quarter, a Consolidated Net Leverage Ratio, as such term is defined in the Credit Agreement and subject to certain conditions contained therein, of no greater than 3.75 to 1.00. The Credit Agreement also permits the Company to establish Key Performance Indicators with respect to certain Environmental, Social and Governance targets of the Company in consultation with JPMorgan as sustainability coordinator, and to enter into an amendment to provide for certain adjustments to the otherwise applicable facility fee and margins based on such indicators. The Credit Agreement also contains customary events of default (including non-payment of principal or interest and breaches of covenants). If any event of default occurs and is not cured within the applicable grace period, the outstanding loans under the facility may be accelerated by lenders and the lenders’ commitments under the Credit Agreement may be terminated. This revolving credit facility backs the Company’s existing commercial paper program and may be used for general corporate purposes.

The descriptions of the provisions of the Credit Agreement are summary in nature and are qualified in their entirety by reference to the full and complete terms of the Credit Agreement, which is filed herewith as Exhibit 10.1.

From time to time, the financial institutions party to the Credit Agreement or their affiliates have performed, and may in the future perform, various commercial banking, investment banking and other financial advisory services for the Company. The Company pays these financial institutions customary fees and expenses for these services. For example, Bank of America, N.A., JPMorgan Chase Bank, N.A., Wells Fargo Bank, N.A. and Goldman Sachs Bank USA or their affiliates serve as dealers under the Company’s commercial paper program. In addition, MUFG Bank, Ltd., Wells Fargo Bank, N.A., and Bank of America, N.A. or their affiliates participate as purchasers and managing agents under the Company’s committed receivables sales facility program.

On March 2, 2023 Xilio Therapeutics, Inc. (Nasdaq: XLO), a biotechnology company developing tumor-activated immuno-oncology therapies for people living with cancer, reported pipeline progress and business updates and reported financial results for the fourth quarter and full year ended December 31, 2022 (Press release, Xilio Therapeutics, MAR 2, 2023, View Source [SID1234628075]).

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"In 2022, we made significant progress against our goals, advancing the clinical development of all three of our novel tumor-activated immuno-oncology programs. Importantly, we observed promising early clinical evidence of our platform in the first two on-treatment tumor samples from patients treated with XTX202, where both the pharmacodynamics in the tumor and in the patients’ peripheral blood were consistent with our expectations for how our tumor-activated molecules are designed to perform," said René Russo, Pharm.D., chief executive officer of Xilio. "In addition, we look forward to several anticipated milestones in 2023, including reporting clinical data from our trials for XTX101, XTX202 and XTX301."

Pipeline and Business Updates

XTX202: tumor-activated, engineered IL-2

XTX202 is an investigational tumor-activated beta-gamma biased (non-alpha), engineered IL-2 molecule designed to potently stimulate CD8+ effector T cells and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). XTX202 is currently being evaluated in an ongoing Phase 1 clinical trial in patients with advanced solid tumors.

● Xilio recently completed dosing patients at the 1 mg/kg dose level (dose level four) and is currently dosing patients at the 1.4 mg/kg dose level (dose level five) in monotherapy dose-escalation (Part 1A) for the Phase 1 clinical trial.
● As of March 1, 2023, a total of 16 patients have been treated with XTX202 in the outpatient setting at five dose levels ranging from 0.27 mg/kg to 1.4 mg/kg once every three weeks (Q3W) in Part 1A for the Phase 1 clinical trial, and monotherapy dose expansion (Part 1B) is open for enrollment.
● No signs of vascular leak syndrome (VLS), including hypotension or decreases in albumin (an early sign of VLS) or hemodynamic compromise, have been observed in patients to date.
● Xilio recently reported preliminary intra-tumoral pharmacokinetics (PK) and pharmacodynamic (PD) data for two patients treated with XTX202, each of whom had an optional on-treatment tumor biopsy and are the only two patients from whom a tumor sample analysis is available to date. For each patient, the tumor sample featured increased numbers of stromal tumor infiltrating

lymphocytes (TILs) and increased frequency of CD8+ effector T cells among these TILs. At the time of the tumor sample, these changes occurred in each patient in the absence of peripheral changes to CD8+ effector T cells demonstrating preliminary evidence of tumor-selective activation.
● A maximum tolerated dose has not yet been determined, and enrollment in Part 1A and Part 1B of the clinical trial is ongoing.

Xilio anticipates multiple milestones for XTX202 through the end of 2023:

● Initiate patient enrollment in a Phase 2 clinical trial evaluating XTX202 as a monotherapy in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma in April 2023.
● Report preliminary anti-tumor activity, safety, PK and PD data from the Phase 1/2 clinical trial in the third quarter of 2023. Xilio anticipates the reported data will include approximately 15-20 patients across a range of solid tumors treated at the 1 mg/kg dose or higher across all cohorts in the Phase 1/2 clinical trial.

XTX301: tumor-activated, engineered IL-12

XTX301 is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram the TME of poorly immunogenic "cold" tumors towards an inflamed, or "hot," state.

● Xilio recently opened clinical trial sites and is actively screening patients for enrollment at a starting dose of 5.0 ug/kg (0.005 mg/kg) in monotherapy dose-escalation for its Phase 1 clinical trial evaluating the safety and tolerability of XTX301 in patients with advanced solid tumors.
● In addition, Xilio anticipates reporting preliminary safety data from the Phase 1 clinical trial into at least the third dose level in the fourth quarter of 2023.

XTX101: tumor-activated anti-CTLA-4

XTX101, an investigational Fc-enhanced, tumor-activated anti-CTLA-4, is currently being evaluated in an ongoing Phase 1 clinical trial in patients with advanced solid tumors.

● As of March 1, 2023, 24 patients have been treated with XTX101 in the Phase 1 clinical trial. Enrollment in monotherapy dose-escalation (Part 1A) has been completed, and enrollment in monotherapy dose-expansion (Part 1B) is ongoing.
● Xilio has determined a recommended Phase 2 dose (RP2D) of 150 mg once every six weeks (Q6W).
● Xilio anticipates reporting preliminary safety, PK, PD and anti-tumor activity data from the Phase 1 clinical trial in the second quarter of 2023.
● In addition, as previously announced, Xilio plans to continue to explore strategic opportunities to advance XTX101 with a partner beyond the current Phase 1 trial.

Upcoming Presentations

Xilio reported the acceptance of the following two abstracts for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, Florida.

Xilio will present a poster highlighting preclinical data demonstrating anti-tumor activity of XTX301 in preclinical mouse models with improved tolerability compared to a systemically active IL-12 molecule.

● Presentation title: A half-life extended, tumor-activated IL-12 increased the infiltration of effector immune cells into the tumor microenvironment and demonstrated anti-tumor activity in syngeneic mouse models.
● Session date and time: Sunday, April 16, 2023, at 1:30 pm to 5:00 pm E.T.
● Abstract number: 587
● Poster Board Number: 21

Xilio will present a poster highlighting preclinical data for a discovery-stage, tumor-activated multi-functional molecule.

● Presentation title: Tumor-activated PD1-directed IL-2 increased antigen specific T cells in tumors and demonstrated anti-tumor activity in mice.
● Session date and time: Sunday, April 16, 2023, at 1:30 pm to 5:00 pm E.T.
● Abstract number: 572
● Poster Board Number: 6

Year-End and Fourth Quarter 2022 Financial Results

● Cash Position: Cash and cash equivalents were $120.4 million as of December 31, 2022, compared to $198.1 million as of December 31, 2021.
● Research & Development (R&D) Expenses: R&D expenses were $15.0 million for the quarter ended December 31, 2022, compared to $11.4 million for the quarter ended December 31, 2021. R&D expenses were $59.2 million for the year ended December 31, 2022, compared to $51.2 million for the year ended December 31, 2021. The year-over-year increase was primarily driven by increased manufacturing, preclinical and clinical development activities for XTX301, increased clinical development activities for XTX202, increased personnel-related costs and increased costs related to the company’s earlier-stage programs. These increases were partially offset by a decrease in manufacturing and preclinical expenses for XTX202 as the program advanced further into clinical development in 2022.
● General & Administrative (G&A) Expenses: G&A expenses were $8.2 million for the quarters ended December 31, 2022 and December 31, 2021, respectively. G&A expenses were $29.9 million for the year ended December 31, 2022, compared to $23.9 million for the year ended December 31, 2021. The year-over-year increase was primarily driven by increased personnel-related costs and an increase in expenses associated with operating as a public company.
● Net Loss: Net loss was $22.5 million for the quarter ended December 31, 2022, compared to $19.7 million for the quarter ended December 31, 2021. Net loss was $88.2 million for the year ended December 31, 2022, compared to $75.8 million for the year ended December 31, 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 second quarter of 2024.

About XTX202 (IL-2) and the Phase 1/2 Clinical Trial

XTX202 is an investigational tumor-activated beta-gamma biased (non-alpha), engineered IL-2 molecule designed to potently stimulate CD8+ effector T cells and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial for XTX202 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. Please refer to NCT05052268 on www.clinicaltrials.gov for additional details.

The planned Phase 2 clinical trial for XTX202 is a multi-center, open-label trial designed to evaluate the safety and anti-tumor activity of XTX202 as a monotherapy in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma at the recommended Phase 2 dose. Please refer to NCT05052268 on www.clinicaltrials.gov for additional details.

About XTX301 (IL-12) and the Phase 1 Clinical Trial

XTX301 is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment (TME) of poorly immunogenic "cold" tumors towards an inflamed, or "hot," state. In November 2022, the U.S. Food and Drug Administration cleared Xilio’s investigational new drug application for the evaluation of XTX301 as a potential treatment for patients with advanced solid tumors.

The Phase 1 clinical trial for XTX301 is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors. Please refer to NCT05684965 on www.clinicaltrials.gov for additional details.

About XTX101 (anti-CTLA-4) and the Phase 1 Clinical Trial

XTX101 is an investigational Fc-enhanced, tumor-activated anti-CTLA-4 monoclonal antibody designed to deplete regulatory T cells when activated (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 XTX101 for the treatment of adult patients with advanced solid tumors. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

On March 2, 2023 Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies for autoimmune diseases and gene therapies, reported financial results for the fourth quarter and full year ended December 31, 2022 and provided a business update (Press release, Selecta Biosciences, MAR 2, 2023, View Source [SID1234628074]).

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"2022 was a successful year for Selecta. We delivered on key milestones across our pipeline and established strategic collaborations that have allowed us to drive forward our development programs," said Carsten Brunn, Ph.D., President and Chief Executive Officer of Selecta. "The Phase 3 DISSOLVE I and II clinical trials investigating SEL-212 in chronic refractory gout remains on track, and we expect to deliver topline data later this quarter. We look forward to the potential for SEL-212 to address the unmet needs of patients suffering from chronic refractory gout. In addition, we are currently enrolling patients in ReiMMAgine, our Phase 1/2 clinical trial of SEL-302 for the treatment of MMA. We intend to continue to leverage learnings from our clinical experience and growing safety database to propel our next-generation programs toward multiple IND filings and advance our wholly owned pipeline using ImmTOR in combination with a proprietary IL-2 (ImmTOR-IL), which we believe has the potential to address the unmet need for precision immunotherapy for autoimmune diseases."

Recent Program Highlights and Anticipated Upcoming Milestones:

Tolerogenic Therapies for Autoimmune Disease:

ImmTOR-IL: In December 2022, the Company selected an identified IL-2 candidate.

The combination of ImmTOR and IL-2 (ImmTOR-IL) represents an evolution of the precision immune tolerance platform, and an opportunity to further advance and expand the Company’s wholly-owned pipeline.
The Company plans to initiate IND enabling studies in 2023, while also exploring multiple autoimmune indications that may be suitable for study with ImmTOR-IL, with an initial focus on diseases of the liver.
Gene Therapies:

SEL-302 for MMA: In December 2022, the Company initiated ReiMMAgine, the Phase 1/2 clinical trial of SEL-302, an adeno-associated virus (AAV) gene therapy combined with ImmTOR for the treatment of MMA.

The ReiMMAgine trial is now enrolling patients and aims to evaluate the safety, tolerability and efficacy of SEL-302.
SEL-018 IgG Protease (Xork) for Late-Onset Pompe Disease: In January 2023, the Company announced an exclusive licensing and development agreement for IdeXork (Xork), a next-generation immunoglobulin G (IgG) protease, to be developed for use with AT845, Astellas Pharma Inc.’s investigational AAV-based treatment for Late-Onset Pompe disease (LOPD) in adults.

Xork is differentiated by its low cross reactivity to pre-existing antibodies in human serum, which the Company believes has the potential to expand access of life-changing gene therapies to more patients.
Under the terms of the agreement, Selecta received a $10M upfront payment and is eligible to receive up to $340M upon the achievement of certain additional development and commercial milestones plus royalties on commercial sales. Selecta is responsible for the early development activities and manufacturing of Xork and will maintain rights to the development of additional indications beyond LOPD.
Biologic Therapies:

SEL-212 for chronic refractory gout: The DISSOLVE I & II Phase 3 clinical trials for SEL-212, which has been licensed to Swedish Orphan Biovitrum AB (publ.) (Sobi), are on track with topline data expected in Q1 2023.

Selecta has been responsible for executing the Phase 3 clinical trials, with reimbursement from Sobi, and Sobi will be responsible for biologics license application filing and commercialization.
ImmTOR with IgA Protease for IgA Nephropathy (IgAN): In December 2022, the Company selected a next generation Immunoglobulin A (IgA) protease from IGAN Biosciences, Inc. to develop in combination with ImmTOR for the treatment of IgAN.

ImmTOR in combination with this new class of IgA protease, which is derived from a commensal bacteria and has low levels of baseline anti-drug antibodies, is designed to address the underlying pathophysiology of IgAN.
The Company plans to initiate IND enabling studies in 2023.
Further Corporate and Partnership Updates:

In November 2022, Blaine Davis was appointed as Chief Financial Officer. Mr. Davis brings more than 25 years of experience in investor relations, business development, corporate affairs and sales and marketing at life sciences companies, with a particular focus on rare diseases.

Fourth Quarter and Full Year 2022 Financial Results:

Cash Position: Selecta had $136.2 million in cash, cash equivalents, marketable securities, and restricted cash as of December 31, 2022, as compared to cash, cash equivalents, marketable securities, and restricted cash of $129.4 million as of December 31, 2021. Selecta believes its available cash, cash equivalents, restricted cash, and marketable securities will be sufficient to meet its operating requirements into mid-2024.

Collaboration and License Revenue: Revenue for the fourth quarter and full year 2022 was $16.8 million and $110.8 million, respectively, as compared to $29.9 million and $85.1 million for the same periods in 2021. Revenue was primarily driven by the license agreement with Sobi resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program.

Research and Development Expenses: Research and development expenses for the fourth quarter and full year 2022 were $19.0 million and $72.4 million, respectively, as compared to $20.3 million and $68.7 million for the same periods in 2021. The quarterly decrease was primarily driven by a decrease in expenses incurred for the SEL-212 clinical program. The annual increase was primarily driven by expenses incurred for preclinical programs, increased personnel expense and stock compensation expense.

General and Administrative Expenses: General and administrative expenses for the fourth quarter and full year 2022 were $6.3 million and $23.9 million, respectively, as compared to $5.5 million and $20.9 million for the same periods in 2021. The quarterly and annual increases were primarily driven by increases in stock compensation and personnel expenses.

Net Income (loss): For the fourth quarter and full year 2022, Selecta reported net income of $5.9 million, or basic net income per share of $0.04, and net income of $35.4 million, or basic net income per share of $0.24, respectively. For the fourth quarter and full year 2021, Selecta reported net income of $12.2 million, or $0.10 per share, and a net loss of $(25.7) million, or $(0.22) per share, respectively.

Conference Call and Webcast Reminder

Selecta’s management will host a conference call at 8:30 AM ET today to provide a corporate update and review the Company’s fourth quarter and full year 2022 financial results. Individuals may participate in the live call via telephone by dialing (844) 845-4170 (domestic) or (412) 717-9621 (international) and may access a teleconference replay for one week by dialing (877) 344-7529 (domestic) or (412) 317-0088 (international) and using confirmation code 8768458. Investors and the public can access the live and archived webcast of this call and a copy of the presentation via the Investors & Media section of the Company’s website, www.selectabio.com.