On April 27, 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 that clinical data from its Phase 3 ROMAN trial of avasopasem for severe oral mucositis will be presented in an oral presentation at the upcoming 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 3-7, 2022 in Chicago, Illinois (Press release, Galera Therapeutics, APR 27, 2022, View Source [SID1234613023]).

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Oral Presentation

Title: ROMAN: Phase 3 trial of avasopasem manganese (GC4419) for severe oral mucositis (SOM) in patients receiving chemoradiotherapy (CRT) for locally advanced, nonmetastatic head and neck cancer (LAHNC)
Abstract Number: 6005
Presenter: Carryn M. Anderson, M.D., University of Iowa Hospitals & Clinics
Session Title: Head and Neck Cancer
Session Date and Time: Friday, June 3, 2022 | 2:45 p.m. – 5:45 p.m. CDT

Galera’s Phase 2 GRECO-2 study of rucosopasem (GC4711) in combination with stereotactic body radiation therapy in pancreatic cancer will also be presented at the ASCO (Free ASCO Whitepaper) meeting in a Trials in Progress poster session.

Poster Presentation

Title: GRECO-2: A randomized, phase 2 study of stereotactic body radiation therapy (SBRT) in combination with rucosopasem (GC4711) in the treatment of locally advanced or borderline resectable nonmetastatic pancreatic cancer
Abstract Number: TPS4184
Presenter: Sarah Hoffe, M.D., H. Lee Moffitt Cancer Center
Session Title: Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary
Session Date and Time: Saturday, June 4, 2022 | 8:00 a.m. – 11:00 a.m. CDT

The titles of the abstracts are currently available in the ASCO (Free ASCO Whitepaper) digital program, with the full abstracts scheduled to be published on May 26, 2022, at 5 p.m. EDT.

On April 27, 2022 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) (BioMarin or the Company) reported financial results for the first quarter ended March 31, 2022 (Press release, BioMarin, APR 27, 2022, View Source [SID1234613039]).

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"We begin 2022 from a position of financial strength including significant contributions from our newest product, Voxzogo, the only approved therapy for children with achondroplasia. We continue to be encouraged by the high level of interest in Voxzogo from families and physicians worldwide seeking treatment that addresses the underlying cause of achondroplasia," said Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin. "As we stated last quarter, in 2022 we expect to return to double-digit revenue growth and profitability. We begin the journey with record first quarter revenues, and foresee continued momentum based on the essential nature of our innovative medicines for our patients around the world."

BioMarin Announces Record Revenues in First Quarter 2022

Mr. Bienaimé continued, "The regulatory team has been working collaboratively with the European Medicines Agency as we near the completion of the application review procedure for potential approval of valoctocogene roxaparvovec gene therapy for the treatment of severe hemophilia A. We remain encouraged by the potential benefit of valoctocogene roxaparvovec for people with severe hemophilia A based on the clinically meaningful study results to date. These demonstrate an 85% reduction in annualized bleeding rates compared to baseline using standard of care. With potential approvals of valoctocogene roxaparvovec in Europe and United States, the continued strong launch of Voxzogo and our anticipated transition to sustainable profitability, we believe 2022 will be a transformational year for all BioMarin stakeholders."

Financial Highlights:

Total Revenues for the first quarter of 2022 were $519.4 million, an increase of 7% compared to the same period in 2021 despite continued erosion of the U.S. Kuvan market. The increase in Total Revenues was primarily attributed to the following:

Higher Vimizim and Naglazyme product revenues primarily driven by new patients initiating therapy and timing of orders in the Middle East and Europe.

Voxzogo commercial sales due to new patients initiating therapy in Europe and the U.S. following regulatory approvals by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) in the third and fourth quarters of 2021, respectively.

Higher Brineura product revenues primarily attributed to new patients initiating therapy in Europe.
These factors were offset by the following:

Lower Aldurazyme product revenues due to timing of bulk lot product fulfillment to Sanofi. BioMarin Aldurazyme revenues are driven by the timing of when the product is released and control is transferred to Sanofi.

Lower Kuvan product revenues primarily due to generic competition as a result of the loss of exclusivity in the U.S. that occurred in October 2020, consistent with expectations.
GAAP Net Income increased to $120.8 million for the first quarter of 2022 compared to GAAP Net Income of $17.4 million for the same period in 2021. The increase was primarily related to the $89.0 million gain, net of tax, on the sale to a third party of the Rare Pediatric Disease Priority Review Voucher (PRV) we received from the FDA in connection with the U.S. approval of Voxzogo and an increase in gross profit.
Non-GAAP Income for the first quarter of 2022 was $105.3 million, essentially flat compared to the same period in 2021. The increase in gross profit was offset by higher sales and marketing expenses to support the commercial launch of Voxzogo and pre-commercialization activities for valoctocogene roxaparvovec and higher research and development expenses driven by the ramp up of activities for early research programs.
Late-stage Regulatory Portfolio (Voxzogo and valoctocogene roxaparvovec)

The global launch of Voxzogo is actively underway, with market access and reimbursement progressing as anticipated. As of March 31, 2022, an estimated 284 children were being treated with commercial Voxzogo globally, 201 from countries outside the United States and 83 within the United States. As of March 31, 2022, there were 15 active markets contributing to Voxzogo sales, including the addition of Saudi Arabia, Slovenia, the Czech Republic, United Arab Emirates and Italy, since the February 2022 update.
Marketing authorization reviews of Voxzogo are in process in Japan and Australia, with potential approvals in those countries in 2022.
During the quarter, the Company provided a top-line update on the Phase 2 randomized, double-blind, placebo-controlled Voxzogo study in infants and young children up to five years of age with achondroplasia. 52-week results trended in favor of Voxzogo compared to placebo on height Z-score, annualized growth velocity, and with no worsening in proportionality in the overall study population. BioMarin intends to initiate discussions with regulatory health authorities to discuss next steps regarding efforts to expand access to Voxzogo treatment for this younger age group. Results from this study are expected to be shared at a scientific meeting mid-year 2022.
The EMA continues the review of BioMarin’s Marketing Authorization Application (MAA) for valoctocogene roxaparvovec and we anticipate a CHMP opinion mid-year 2022. BioMarin has provided the EMA with two-year follow-up safety and efficacy data from the GENEr8-1 study.
Based on the favorable results from the two-year follow-up safety and efficacy data from the GENEr8-1 study, BioMarin is targeting a BLA resubmission for valoctocogene roxaparvovec in June 2022 followed by an expected 6-month review procedure by the FDA. A pre-submission interaction is scheduled with the FDA later this quarter to discuss BioMarin’s BLA resubmission efforts.
During the first quarter of 2022, the Company announced that a subject treated with valoctocogene roxaparvovec in the Phase 2 study over 5 years ago reported a salivary gland mass in late 2021. The event was reported as unrelated to valoctocogene roxaparvovec by the investigator. The subject was successfully treated, and the Company conducted a genomic analysis from a tissue sample containing the mass. Today, BioMarin announced that the findings from the completed analysis showed a comparable pattern of integration between healthy and tumor containing tissues, with no evidence emerging that vector integration contributed to the salivary gland mass. These data will be presented both in a workshop of the annual American Society of Gene & Cell Therapy meeting and the World Federation of Hemophilia 2022 World Congress in May, supplied to the EMA as part of the ongoing review of the MAA and included in the BLA resubmission.
Earlier-stage Development Portfolio (BMN 255, BMN 331, BMN 351, BMN 349, BMN 293 (DiNA-001))

BMN 255 for primary hyperoxaluria type 1, a subset of chronic renal disease: The Company has completed the single ascending dose arm of the First-in-Human study and is analyzing the results. BioMarin believes the availability of a potent, orally bioavailable, small molecule like BMN 255 may be able to significantly reduce disease and treatment burden in certain people with chronic renal disease.
BMN 331 gene therapy product candidate for Hereditary Angioedema (HAE): The Company announced that it has begun dosing patients in the Phase 1/2 HAERMONY study to evaluate BMN 331, an investigational AAV5-mediated gene therapy for people living with hereditary angioedema (HAE). The FDA granted Orphan Disease Designation status to BMN 331 in 2021.
BMN 351 for Duchenne Muscular Dystrophy (DMD): IND-enabling studies continue with BMN 351, an antisense oligonucleotide therapy for individuals with exon 51-skip-amenable DMD. BMN 351 was developed using familiar chemistry and superior biology, by targeting a novel, upstream, splice enhancer site demonstrating improved binding affinity and tolerability in preclinical models. Preclinical data suggest that restored expression of near-full-length dystrophin protein at levels of up to 40% will convert phenotypes from rapid loss to durable preservation of strength and ambulation. BioMarin expects to file an IND for BMN 351 in the first half of 2022, and anticipates treating clinical trial participants with Duchenne muscular dystrophy in the fourth quarter of 2022.
BMN 349 for alpha-1 antitrypsin deficiency: Preclinical studies have demonstrated that BMN 349 is an orally bioavailable, small molecule that is titratable with rapid onset and high potency and efficacy. Preclinical results have strong implications for potential improvement of current management, particularly for severe liver disease requiring rapid action. BioMarin’s goal is to file the IND in the second half of 2023.
BMN 293 (formerly DiNA-001) for MYBPC3 hypertrophic cardiomyopathy (HCM): Preclinical studies are underway with BMN 293 following a collaboration announced in 2020 with DiNAQOR, a gene therapy platform company, to develop novel gene therapies to treat rare genetic cardiomyopathies. Mutations in MYBPC3 are the most common cause of inherited HCM. Early investigations suggest that gene therapy-mediated gene transfer can lead to widespread expression of the gene product, cardiac myosin-binding protein C (MyBP-C), in cardiac tissue, which can normalize relaxation kinetics and potentially ameliorate the disease phenotype in individuals suffering from cardiomyopathy. BioMarin’s goal is to file the IND in 2023.
2022 Full-Year Financial Guidance (in millions, except %)

(1) All Financial Guidance items are calculated based on U.S. GAAP with the exception of Non-GAAP
Income. Refer to Non-GAAP Information beginning on page 9 of this press release for a complete discussion of the Company’s Non-GAAP financial information and reconciliations to the corresponding GAAP reported information.

BioMarin will host a conference call and webcast to discuss first quarter and year to date 2022 financial results today, Wednesday, April 27, 2022 at 4:30 p.m. ET. This event can be accessed on the investor section of the BioMarin website at www.biomarin.com.

On April 27, 2022 Pacira BioSciences, Inc. (NASDAQ:PCRX) reported that it will report its first quarter financial results before the open of the U.S. markets on Wednesday, May 4, 2022 (Press release, Pacira Pharmaceuticals, APR 27, 2022, View Source [SID1234613055]). Following the release, the company will host a live conference call and webcast at 8:30 a.m. ET.

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To participate in the conference call, dial 1-877-845-0779 and provide the passcode 4063578. International callers may dial 1-720-545-0035 and use the same passcode. In addition, a live audio of the conference call will be available as a webcast. Interested parties can access the event through the "Events" page on the Pacira website at investor.pacira.com.

For those unable to participate in the live call, a replay will be available at 1-855-859-2056 (domestic) or 1-404-537-3406 (international) using the passcode 4063578. The replay of the call will be available for one week from the date of the live call. The webcast will be available on the Pacira website for approximately two weeks following the call.

On April 27, 2022 Repertoire Immune Medicines announced today that Science Advances published preclinical research demonstrating the company’s cell-tethering technology can deliver the potent cytokine interleukin-12 (IL-12) to solid tumors without eliciting the severe systemic toxicities typically associated with the use of this cytokine (Press release, Repertoire, APR 27, 2022, View Source [SID1234613072]). The research, conducted in mouse models, found that the use of cell-tethered IL-12 elevated anti-tumor activity in the immunosuppressive tumor microenvironment (TME).

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"A tumor has multiple mechanisms that help it avoid recognition and elimination by the immune system. These defense mechanisms remain a major challenge for cellular immunotherapies to achieve a durable clinical response," said Anthony Coyle, Ph.D., President, Research and Development, Repertoire Immune Medicines. "In this preclinical research, Repertoire’s cell-tethering technology delivered dose-controlled amounts of IL-12 onto the surface of tumor-targeted T cells. These IL-12-tethered T cells were associated with pronounced repolarization of the tumor microenvironment, ultimately resulting in enhanced T cell response, which has the potential to improve the efficacy of the cellular immunotherapies."

Tumors have immunosuppressive microenvironments that can limit the efficacy of cellular immunotherapies used in cancer treatment. Immune-stimulating cytokines such as IL-12 have been shown to counter the immunosuppressive conditions within the tumor. However, the dose of IL-12 required to achieve these beneficial effects has been associated with severe systemic toxicities.

In the publication, "Cell-surface tethered IL-12 repolarizes the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy," Repertoire’s tethering technology achieved direct and localized delivery of IL-12 to tumors without systemic toxicities. The use of tethered IL-12 was also associated with repolarization of myeloid-derived suppressor cells into activated inflammatory monocytes that support anti-tumor activity in the TME.

Repertoire is currently investigating the use of cell-tethered IL-12 in an ongoing Phase 1 study of its investigational candidate RPTR-168 for human papillomavirus-positive tumors.

About RPTR-168

RPTR-168 is an autologous multi-targeted T cell (MTC) therapeutic candidate derived from rare peripheral blood T cells. The T cells are collected from each patient through apheresis and are primed and expanded by a set of five tumor-associated antigens known to be expressed on human papillomavirus (HPV)-16-positive tumors. RPTR-168 is designed to deliver interleukin-12 (IL-12), a potent immunomodulatory agent that has been shown to improve anti-tumor activity by promoting T cell function inside the tumor microenvironment.

On April 27, 2022 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that four abstracts highlighting selinexor clinical research have been selected for presentation, including one oral presentation, at the upcoming 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 3-7, 2022, in Chicago (Press release, Karyopharm, APR 27, 2022, View Source [SID1234613024]).

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Research findings to be presented include an oral presentation discussing subgroup analyses and molecular classification data from the Phase 3 SIENDO study evaluating selinexor in endometrial cancer and a poster presentation highlighting preliminary results from a Phase 1/2 study evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis.

"At Karyopharm, we are laser focused on targeting cancers with high unmet need where our science enables us to make the biggest difference in the lives of patients," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "We are excited to share the latest research at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting as these data underscore the innovation across our four core programs in clinical development."

Details for the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting presentations are as follows:

Oral Presentation

Title: Randomized phase III study of maintenance selinexor versus placebo in endometrial cancer (ENGOT – EN5/GOG-3055/SIENDO): Impact of subgroup analysis and molecular classification
Presenter: Vicky Makker, Memorial Sloan Kettering Cancer Center
Abstract #: 5511
Date and time: Tuesday, June 7, 2022, 8:00 a.m. – 9:30 a.m. CDT
Session: Clinical Science Symposium/Molecular-Based Treatment for Endometrial Cancer

Poster Presentations
Title: A phase 1, open-label, dose-escalation study of selinexor plus ruxolitinib in patients with treatment-naïve myelofibrosis
Presenter: Haris Ali, City of Hope
Abstract #: 7060
Date and time: Saturday, June 4, 2022, 8:00 a.m. – 11:00 a.m. CDT
Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Title: Phase 1b study of weekly split-dose selinexor in soft tissue sarcoma (STS)
Presenter: Abdulazeez Salawu, University Health Network
Abstract #: 11563
Date and time: Sunday, June 5, 2022, 8:00 a.m. – 11:00 a.m. CDT
Session: Sarcoma

Title: Digital monitoring and assessments in patients with glioblastoma
Presenter: Yasaman Damestani, Karyopharm Therapeutics, Inc.
Abstract #: 2045
Date and time: Sunday, June 5, 2022, 8:00 a.m. – 11:00 a.m. CDT
Session: Central Nervous System Tumors

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 a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea, Singapore and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including Multiple Myeloma, 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]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).

For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
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 were 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.