On December 12, 2022 Amgen (NASDAQ:AMGN) reported that it will host a webcast call for the investment community following the announced acquisition of Horizon Therapeutics at 8:00 a.m. ET on Monday, December 12, 2022 (Press release, Amgen, DEC 12, 2022, View Source [SID1234625080]). Robert A. Bradway, chairman and chief executive officer, along with members of the executive team, will participate.

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The webcast will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

The directors of Amgen accept responsibility for the information contained in this press release. To the best of the knowledge and belief of the directors (who have taken all reasonable care to ensure that such is the case), the information contained in this press release is in accordance with the facts and does not omit anything likely to affect the import of such information.

On December 12, 2022 ALX Oncology Holdings Inc., ("ALX Oncology") (Nasdaq: ALXO), a clinical-stage immuno-oncology company developing therapies to block the CD47 checkpoint pathway, reported the presentation of clinical data from the Phase 1a dose escalation part of the ASPEN-05 trial evaluating evorpacept in combination with azacitidine and venetoclax for the treatment of patients with relapsed or refractory ("r/r") or newly diagnosed ("ND") acute myeloid leukemia ("AML") (Press release, ALX Oncology, DEC 12, 2022, View Source [SID1234625079]). The new results, shared in a poster at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting [Abstract #4076], show that the combination of evorpacept with azacitidine and venetoclax is active and generally well tolerated. As of October 3, 2022, 14 patients with either r/r or ND AML have been treated with evorpacept in the Phase 1 dose escalation part of the study, administered at 20 mg/kg or 30 mg/kg once every 2 weeks ("Q2W") or 60 mg/kg once every 4 weeks ("Q4W") together with standard dosing of azacitidine and venetoclax.

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Evorpacept in combination with azacitidine and venetoclax was generally well tolerated (N=14) with no maximum tolerated dose identified and a maximum administered dose of 60 mg/kg Q4W.

In 10 relapsed or refractory AML response-evaluable patients, including 8 that had progressed after prior venetoclax treatment, all experienced a reduction in bone marrow blasts, and 4 achieved a response.

In 3 newly diagnosed AML response-evaluable patients, all 3 achieved a response, including 1 complete response ("CR"), 1 CR with incomplete hematologic recovery ("CRi"), and 1 morphologic leukemia free state ("MLFS").
"It is extremely encouraging to observe evorpacept’s preliminary clinical activity in a population of difficult to treat AML patients with primarily relapsed or refractory disease after prior venetoclax therapy, as well as TP53 mutation and adverse risk genetics," said Harry Erba M.D., Director of the Leukemia Program in the Division of Hematologic Malignancies and Cellular Therapy at Duke University, Durham, NC. "Additionally, evorpacept’s favorable initial tolerability profile in combination with azacitidine and venetoclax suggests it may be safely added to this AML backbone therapy without worsening cytopenias, which is particularly important for this patient population."

"The initial data from this early part of the ASPEN-05 study support the tolerability and activity of evorpacept in patients with AML, and provide further validation for adding our CD47 myeloid checkpoint blocker to established backbone regimens in patients with cancer," said Sophia Randolph M.D., Ph.D., Chief Medical Officer, ALX Oncology. "We are pleased to see this initial data as part of our ongoing studies of evorpacept in both solid tumor indications and hematologic malignancies, which support the emerging role of CD47-blockade in enhancing the innate immune anti-cancer response."

Conference Call on December 13th at 7:30 a.m. EST

ALX Oncology will host a conference call on Tuesday, December 13, 2022 at 7:30 a.m. EST to further discuss the initial AML data from ASPEN-05. In addition to ALX Oncology’s executive management team, Harry Erba M.D., Director of the Leukemia Program in the Division of Hematologic Malignancies and Cellular Therapy at Duke University, Durham, NC will be featured on the call to discuss the results.

To access the conference call, please dial (800) 715-9871 (U.S./Canada) or (646) 307-1963 (international) at least 10 minutes prior to the start time and refer to conference ID 1300143. Presentation slides will be available to download under "News & Events (see "Events") in the Investors section of the ALX Oncology website at www.alxoncology.com.

On December 11, 2022 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism pioneering therapies for rare diseases, reported new data from the ongoing extension study assessing the long-term efficacy and safety of PYRUKYND (mitapivat) in adults with pyruvate kinase (PK) deficiency who had participated in one of the pivotal studies, ACTIVATE and ACTIVATE-T, conducted in not regularly transfused and regularly transfused adults with PK deficiency, respectively (Press release, Agios Pharmaceuticals, DEC 12, 2022, View Source [SID1234625078]). Data from the studies were featured in multiple presentations at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, hosted Dec. 10-13, 2022, in New Orleans. PYRUKYND is a first-in-class, oral PK activator and the first approved disease-modifying therapy for patients in the U.S. and EU with this rare, debilitating, lifelong hemolytic anemia.

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Long-term extension data (abstract # 2328) show that previously reported effects of PYRUKYND on hemoglobin and transfusion burden were maintained over time. As of the March 27, 2022 data cut-off, the median duration of hemoglobin response among the 31 hemoglobin responders from ACTIVATE and the long-term extension study was 18.3 months, with responses ongoing up to 32.9 months. Hemoglobin response rate among patients who switched from placebo in ACTIVATE to PYRUKYND in the extension study (39.5 percent Hb response rate) was similar to that observed in patients treated with PYRUKYND in ACTIVATE. All regularly transfused patients who achieved transfusion-free status in ACTIVATE-T with PYRUKYND treatment maintained transfusion-free status through the extension study for up to 38.3 months. PYRUKYND was well tolerated, and the safety profile was consistent with that in ACTIVATE and ACTIVATE-T, as well as previous studies.

"PYRUKYND is the first oral agent that has the potential to improve symptoms and long-term complications of PK deficiency in adult patients," said Rachael Grace, M.D., MMSc, director of hematology clinical research at Boston Children’s Hospital and investigator on the long-term extension study. "People living with PK deficiency experience a wide range of complications throughout their lives, including osteopenia, iron overload and pulmonary hypertension, many of which occur at earlier ages than would be expected. We are encouraged by the long-term extension data reported today and look forward to researching the efficacy and safety of PYRUKYND in the ACTIVATE-Kids and ACTIVATE-KidsT studies in pediatric PK deficiency patients who are not regularly transfused and are regularly transfused, respectively."

"Collectively, the data we have presented at ASH (Free ASH Whitepaper) continue to demonstrate the benefits of long-term treatment with PYRUKYND for adults with PK deficiency, including improvements in hemoglobin, transfusion burden, iron overload and patient-reported outcomes," said Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios. "In addition to progressing our pivotal trials in pediatric patients, we are encouraged by the results from the long-term extension study of our Phase 2 study of PYRUKYND in both alpha- and beta-thalassemia, which we also presented at ASH (Free ASH Whitepaper), and believe the consistency of the data between indications further supports the potential of PYRUKYND to make a positive impact across rare blood disorders with similar underlying pathophysiology."

Agios also presented data at ASH (Free ASH Whitepaper) further supporting the potential of PYRUKYND to address hallmark symptoms and complications of PK deficiency. More details on the presentations are provided below and on the ASH (Free ASH Whitepaper) 2022 page on Agios.com.

Long-term Improvements in Patient-reported Outcomes in Patients with Pyruvate Kinase Deficiency Treated with Mitapivat (Abstract #506)
In an oral presentation, data from ACTIVATE, ACTIVATE-T and the long-term extension study were reported, showing that treatment with PYRUKYND was associated with long-term, durable and clinically meaningful improvements in signs, symptoms and functional impacts, irrespective of transfusion status. Patient-reported outcome (PRO) improvements among patients treated with PYRUKYND were sustained over time in the long-term extension (LTE) study through Week 84. At Week 84 of the LTE study, clinically meaningful improvements in PROs mean scores were achieved in more than half of patients. These results suggest that by improving health-related quality of life, treatment with PYRUKYND may provide meaningful patient-centric benefits.

Mitapivat Improves Iron Overload in Patients with Pyruvate Kinase Deficiency (Abstract #1021)
In a poster presentation, data from ACTIVATE and the long-term extension study were reported that showed meaningful long-term improvements in key systemic regulators of iron homeostasis and measures of iron overload – including erythroferrone, soluble transferrin receptor (sTfR) and hepcidin – continued up to 96 weeks in patients treated with PYRUKYND. Additionally, patients treated with PYRUKYND who had evidence of iron overload at baseline showed clinically meaningful and continued improvements in iron overload over time as measured by liver iron concentration (median [Q1, Q3] decrease from baseline to Week 96 of PYRUKYND treatment of –1.95 [–4.85, –0.70] mg Fe/g dw). Ferritin levels remained stable across both patient groups treated with PYRUKYND or placebo.

Mitapivat Improves Markers of Hemolysis and Erythropoiesis in Patients with Pyruvate Kinase Deficiency Irrespective of Hemoglobin Response (Abstract #3644)
In a separate poster presentation, data from the ACTIVATE study were reported showing that treatment with PYRUKYND improved markers of hemolysis and ineffective erythropoiesis in adults with PK deficiency. The analysis also shows that directional improvements occur even in patients who did not achieve the clinical trial definition of hemoglobin response.

PYRUKYND was approved in February 2022 by the U.S. Food and Drug Administration (FDA) and received marketing authorization in November 2022 by the European Medicines Agency (EMA) for adults with PK deficiency. Both the FDA and EMA have granted orphan drug designation to PYRUKYND in PK deficiency. In addition, PYRUKYND has been granted FDA orphan drug designation for the treatment of thalassemia and sickle cell disease, for which enrollment for ongoing pivotal studies is underway.

Conference Call Information
Agios will host a live investor event on Dec. 12, 2022, at 7:00 a.m. CT in New Orleans to review the key clinical oral and poster presentations from this year’s ASH (Free ASH Whitepaper) meeting. The event will be webcast live and can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

About PK Deficiency
Pyruvate kinase (PK) deficiency is a rare, inherited disease that presents as chronic hemolytic anemia, which is the accelerated destruction of red blood cells. The inherited mutation in the PKLR gene can cause a deficit in energy within the red blood cell, as evidenced by lower PK enzyme activity, a decline in adenosine triphosphate (ATP) levels and a build-up of upstream metabolites, including 2,3-DPG (2,3-diphosphoglycerate).

PK deficiency is associated with serious complications, including gallstones, pulmonary hypertension, extramedullary hematopoiesis, osteoporosis and iron overload and its sequelae, which can occur regardless of the degree of anemia or transfusion burden. PK deficiency can also cause quality of life problems, including challenges with work and school activities, social life and emotional health. Current management strategies for PK deficiency, including red blood cell transfusions and splenectomy, are associated with both short- and long-term risks. For more information, please visit www.knowpkdeficiency.com.

About PYRUKYND (mitapivat)
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the United States, and for the treatment of PK deficiency in adult patients in the European Union.

IMPORTANT SAFETY INFORMATION
Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.

Adverse Reactions: Serious adverse reactions occurred in 10% of patients receiving PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which occurred in 1 patient. In the ACTIVATE trial, the most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia.

Drug Interactions:

Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.

Please see full Prescribing Information and Summary of Product Characteristics for PYRUKYND.

On December 12, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported updated results from the Phase 1 portion of its study evaluating the safety and efficacy of once-weekly selinexor in combination with standard dose ruxolitinib in patients with treatment-naïve myelofibrosis (NCT04562389) (Press release, Karyopharm, DEC 12, 2022, View Source [SID1234625073]). The data, featured in a poster presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) 2022 Annual Meeting and Exposition, show that the combination of selinexor with ruxolitinib achieved rapid and sustained spleen responses, encouraging improvements in symptoms and stabilization of hemoglobin levels in patients with treatment-naïve myelofibrosis.

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As of October 21, 2022, 24 patients had been assigned to either a 40 mg or 60 mg once weekly dose of selinexor, in combination with ruxolitinib 15/20 mg BID (twice daily). At week 24, 92% of efficacy evaluable patients (11 out of 12) demonstrated ≥35% reduction in spleen volume (SVR35). Ongoing reductions in SVR were seen from baseline to week 12 and week 24, with a 45% median reduction at week 12 and a 49% median reduction at week 24. 67% of the evaluable patients for symptom response (4 out of 6) at week 24 achieved ≥50% reduction (TSS50). 57% of transfusion-independent patients (13 out of 23) maintained or improved their hemoglobin levels.

"As an oral agent with a unique mechanism of action, selinexor has previously shown single-agent activity in myelofibrosis patients," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "As a result, we believe that the combination of selinexor and ruxolitinib has the potential to meaningfully build upon the current standard of care, which is ruxolitinib alone, for patients with treatment-naïve myelofibrosis. We look forward to further developing this combination in the randomized phase of the study."

The safety population was comprised of 24 patients, all of whom received at least one dose of selinexor. The most common adverse events (AEs) were nausea (75%), anemia (62%) and fatigue (58%), the majority of which were grades 1-2. The most common reported grade 3-4 treatment-emergent AEs were anemia (37%) and thrombocytopenia (21%), both of which were reversible.

"In the Phase 1 portion of the study, encouraging efficacy was observed across the relevant efficacy endpoints of SVR35, TSS50, and hemoglobin stabilization and a generally manageable safety profile was observed regardless of dose. Furthermore, I find the rapid spleen reduction as early as week 12 especially notable, along with early signs of durability," said Dr. Haris Ali, City of Hope Comprehensive Cancer Center. "These data support the potential of an oral XPO1 inhibitor, in combination with a JAK inhibitor, to deliver significant benefits for patients with myelofibrosis."

Investor and Analyst Event on Selinexor Data in Patients with Treatment-Naïve Myelofibrosis at ASH (Free ASH Whitepaper) 2022

Karyopharm will host a webcast today, December 12, 2022, at 8:30 a.m. Eastern Time (7:30 a.m. CT local time), featuring key opinion leaders Dr. Haris Ali, City of Hope Comprehensive Cancer Center and Dr. Srdan Verstovsek, MD Anderson Cancer Center. Drs. Ali and Verstovsek will discuss the updated data on selinexor in combination with ruxolitinib as well as the current treatment landscape and unmet medical need in treating patients with myelofibrosis, respectively.

To access the event, the live audio webcast and slides will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website following the event.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by Karyopharm’s partners, Antengene, Menarini, Neopharm and FORUS in China, South Korea, Singapore, Australia, Hong Kong, Germany, Austria, Israel and Canada.

Please refer to the local Prescribing Information for full details.

Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.

Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.

Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.

Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.

Serious Infection: Monitor for infection and treat promptly.

Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.

Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.

Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.

The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.
For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.

On December 12, 2022 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, reported the submission of its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for avasopasem for radiotherapy-induced severe oral mucositis (SOM) in patients with head and neck cancer (HNC) undergoing standard-of-care treatment (Press release, Galera Therapeutics, DEC 12, 2022, View Source [SID1234625072]). The FDA has granted Fast Track and Breakthrough Therapy designations to avasopasem for the reduction of SOM induced by radiotherapy. SOM is characterized by the inability to eat solid food or drink liquids and may require the surgical placement of feeding tubes to maintain nutrition and hydration. There are currently no FDA-approved drugs to reduce SOM for these patients.

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"With submission of this NDA, we achieved an important milestone towards our goal of transforming radiotherapy, potentially bringing patients with HNC the first approved drug for SOM and relief from its tremendous burden," said Mel Sorensen, M.D., President and Chief Executive Officer of Galera Therapeutics. "Approximately 42,000 patients with HNC undergo standard-of-care radiotherapy every year in the U.S. and are at risk of developing SOM. Our two rigorous, placebo-controlled trials which enrolled nearly 700 patients give us confidence that avasopasem has the potential to provide meaningful clinical benefit for patients by reducing SOM incidence, days, and severity while also delaying its onset. We look forward to working closely with the FDA during the review process."

Dr. Sorensen continued, "Further, the reduction in cisplatin-related chronic kidney disease in patients treated with avasopasem reported in October may offer added clinical benefit to the large number of patients with HNC who receive cisplatin with their radiotherapy."

The NDA is supported by the randomized, double-blinded, placebo-controlled Phase 3 ROMAN and Phase 2b GT-201 trials which enrolled a total of 678 patients. Results from the 455-patient ROMAN trial demonstrated a clinically meaningful reduction in patients’ SOM burden across multiple endpoints, with statistically significant reductions on the primary endpoint of incidence of SOM and the secondary endpoint of number of days of SOM, more than halving the median number of days a patient suffered SOM. Avasopasem also showed clinically meaningful reductions in severity of SOM (Grade 4 incidence) compared to placebo. Exploratory analyses, such as time to SOM onset and SOM incidence at various landmarks of radiotherapy delivered, further demonstrated the clinical benefit of avasopasem in reducing the burden of SOM. Avasopasem was generally well tolerated compared to placebo. Overall, the adverse event (AE) incidences noted in the clinical trials were consistent with the interpretation that avasopasem was not associated with a clinically meaningful increase in the AE profile expected for the target patient population receiving standard-of-care chemoradiation therapy. In addition, a prospectively defined exploratory analysis looking at renal function through 12 months follow-up showed that avasopasem reduced cisplatin-induced chronic kidney disease by 50%.

About the Phase 3 Roman Trial

The Phase 3 ROMAN trial (GTI-4419-301) was a randomized, double-blind, placebo-controlled trial in 455 patients designed to evaluate the ability of avasopasem to reduce radiation-induced SOM in patients with locally advanced HNC, receiving seven weeks of standard-of-care radiotherapy plus cisplatin. Patients were randomized to one of the two treatment groups (3:2) to receive 90 mg of avasopasem or placebo by infusion on the days they receive their radiation treatment.

Results from the 455-patient ROMAN trial demonstrated a meaningful reduction in patients’ SOM burden across multiple endpoints, with statistically significant reductions on the primary endpoint of incidence of SOM and the secondary endpoint of number of days of SOM, more than halving the median number of days a patient suffered SOM. Meaningful reduction in the number of patients who developed the most severe form of SOM (Grade 4) was also observed. Exploratory analyses, such as time to SOM onset and SOM incidence at various landmarks of radiotherapy delivered, also demonstrated the clinical benefit of avasopasem in reducing the burden of SOM, along with a reduction in long-term loss of kidney function associated with concurrent cisplatin. Avasopasem was generally well tolerated compared to placebo.

About the Phase 2b GT-201 Trial

The GT-201 trial (GTI-4419-201) was a randomized, double-blind, placebo-controlled trial in 223 patients designed to evaluate the ability of avasopasem to reduce radiation-induced SOM in patients with locally advanced HNC, receiving seven weeks of standard-of-care radiotherapy plus cisplatin. Patients were randomized to one of the three treatment groups (1:1:1) to receive either 30 mg or 90 mg of avasopasem or placebo by infusion on the days they receive their radiation treatment.

Results from the 223-patient Phase 2b trial demonstrated a meaningful reduction in patients’ SOM burden across multiple endpoints, with a statistically significant reduction on the primary endpoint of number of days of SOM in the 90 mg avasopasem arm compared to placebo. Avasopasem also resulted in clinically meaningful reductions in the incidence, severity (Grade 4 incidence), and onset of SOM compared to placebo. Avasopasem was generally well tolerated compared to placebo. The FDA granted Breakthrough Therapy designation to avasopasem for the reduction of SOM induced by radiotherapy, based on the positive results of the GT-201 trial.

About Severe Oral Mucositis (SOM)

Approximately 42,000 patients with head and neck cancer undergo standard-of-care radiotherapy every year in the U.S. and are at risk of experiencing SOM. In patients with head and neck cancer, radiotherapy is a mainstay of treatment. Approximately 70 percent of patients receiving radiotherapy for head and neck cancer develop SOM, defined by the inability to eat solid food or drink liquids. The impact on patients who develop SOM is substantial, particularly when hospitalization and/or surgical placement of feeding (PEG) tubes to maintain nutrition and hydration are required. SOM can adversely affect cancer treatment outcomes by causing interruptions in radiotherapy, which may compromise the otherwise good prognosis for tumor control in many of these patients. There is currently no drug approved to prevent or treat SOM for these patients.

About Avasopasem

Avasopasem manganese 90 mg (avasopasem, or GC4419) is a selective small molecule dismutase mimetic in development for the reduction of radiotherapy-induced severe oral mucositis (SOM) in patients with locally advanced head and neck cancer (HNC) and for the reduction of radiotherapy-induced esophagitis in patients with lung cancer. The FDA has granted Fast Track and Breakthrough Therapy designations to avasopasem for the reduction of SOM induced by radiotherapy.