On September 27, 2022 Seagen Inc. (Nasdaq: SGEN), a world leader and pioneer in antibody-drug conjugate (ADC) therapies, and Zai Lab Limited (Nasdaq: ZLAB; HKEX: 9688), a patient-focused, innovative, commercial-stage global biopharmaceutical company, reported an exclusive collaboration and license agreement for the development and commercialization of TIVDAK (tisotumab vedotin-tftv) in mainland China, Hong Kong, Macau, and Taiwan (Press release, Seagen, SEP 27, 2022, View Source [SID1234621455]). TIVDAK is the first and only ADC approved in the U.S. for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

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Under the terms of the agreement, Seagen will receive an upfront payment of $30 million, as well as development, regulatory, and commercial milestone payments, and tiered royalties on net sales of TIVDAK in the Zai Lab territory. Based on the existing TIVDAK co-development and co-commercialization collaboration between Seagen and Genmab (Nasdaq: GMAB), all upfront, milestone payments, and royalties will be shared 50/50 with Genmab.

In 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval for TIVDAK for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. As verification and description of clinical benefit in the U.S., and to support further global regulatory applications, a confirmatory phase 3 open-label, randomized, global clinical trial, innovaTV 301, is ongoing.

"This agreement enables us to leverage Zai Lab’s strong expertise in developing and commercializing innovative medicines in the licensed territory," said Natasha Hernday, EVP Corporate Development and Alliance Management, Seagen. "We are delighted to collaborate with Zai Lab, including on the phase 3 innovaTV 301 trial, an important component of expanding the availability of TIVDAK to recurrent or metastatic cervical cancer patients around the world. TIVDAK is also under evaluation and development in early trials for first-line cervical cancer and certain other solid tumors."

"Zai Lab has a significant presence treating women’s cancers in China, and TIVDAK is an important addition to our oncology commercial portfolio. Treatments for cervical cancer remain a significant unmet need in China with approximately 110,000 new cases annually 1, and currently there are few effective therapeutic options available," said William Liang, Chief Commercial Officer, President of Greater China at Zai Lab. "We look forward to this collaboration with Seagen to make TIVDAK available for patients in China as we expand our oncology portfolio."

"Following progression on first-line standard of care therapy, there are limited treatment options, and chemotherapy has low objective response rates with poor outcomes," said Dr. Lingying Wu, Director of the Department of Gynecologic Oncology, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. "This represents one of the biggest challenges faced by gynecologic oncologists with significant unmet needs for new therapies. We believe TIVDAK could become an important treatment option for patients with cervical cancer in China, as it demonstrated clinically meaningful, durable responses with a tolerable safety profile."

About Cervical Cancer in China

Cervical cancer remains one of the leading causes of cancer death in women in China and globally. An estimated 110,000 new cases of cervical cancer occur annually in China1. Treatment options are limited for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. TIVDAK is currently not approved in this region and is well positioned to provide a new option for previously treated advanced cervical cancer patients who currently have limited treatment options and poor outcomes.

About TIVDAK (tisotumab vedotin-tftv)

TIVDAK (tisotumab vedotin-tftv) is an ADC composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggests that the anticancer activity of TIVDAK is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, TIVDAK also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

Please see Important Safety Information below.2

TIVDAK (tisotumab vedotin-tftv) for injection, for intravenous use, 40 mg Important Safety Information

BOXED WARNING: OCULAR TOXICITY

TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

Warnings and Precautions

Ocular Adverse Reactions occurred in 60% of patients with cervical cancer treated with TIVDAK. The most common were conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%). Grade 3 ocular adverse reactions occurred in 3.8% of patients, including severe ulcerative keratitis in 3.2% of patients. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose.

In innovaTV 204, 4% of patients experienced visual acuity changes to 20/50 or worse, including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75% resolved, including the patient who experienced decreased visual acuity to 20/200.

Refer patients to an eye care provider for an ophthalmic exam including visual acuity and slit lamp exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold dose, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

Peripheral neuropathy (PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (11%), peripheral sensorimotor neuropathy (5%), motor neuropathy (3%), muscular weakness (3%), and demyelinating peripheral polyneuropathy (1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barré syndrome.

Monitor patients for signs and symptoms of neuropathy. For new or worsening PN, withhold, dose reduce, or permanently discontinue TIVDAK based on the severity of PN.

Hemorrhage occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients.

Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.

Pneumonitis: Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced pneumonitis, including 1 patient who had a fatal outcome.

Monitor patients for pulmonary symptoms indicative of pneumonitis. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.

Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.

Embryo-fetal toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock, pneumonitis, sudden death, and multisystem organ failure (each 1%).

Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

In the innovaTV 204 study, the most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

Drug interactions

Strong CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.

Use in Specific Populations

Moderate or Severe Hepatic Impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.

Please see full prescribing information, including BOXED WARNING for TIVDAK here.

About the Seagen and Genmab Collaboration

TIVDAK (tisotumab vedotin) is being co-developed and co-commercialized by Genmab and Seagen under an agreement in which the companies, with respect to certain major markets, including China, share costs and profits for the product on a 50/50 basis, including upfront payments, future milestones and royalties received under the collaboration and licensing agreement with Zai Lab.

On September 27, 2022 Celularity Inc. (Nasdaq: CELU) ("Celularity"), a clinical-stage biotechnology company developing placental-derived allogeneic cell therapies, reported that Robert Hariri, M.D., Ph.D., Founder, Chairman and Chief Executive Officer of Celularity, will present at the Jefferies Cell and Genetic Medicine Summit on Friday, September 30, 2022 at 11 a.m. ET (Press release, Celularity, SEP 27, 2022, View Source;utm_medium=rss&utm_campaign=celularity-to-present-at-jefferies-cell-and-genetic-medicine-summit [SID1234621454]).

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A live webcast of the presentation can be accessed on the Investors section of Celularity’s website at View Source A replay of the webcast will be archived and available following the event for approximately 30 days.

On September 27, 2022 Cardinal Health (NYSE: CAH) reported to release first-quarter financial results for its fiscal year 2023 on November 4, prior to the opening of trading on the New York Stock Exchange (Press release, Cardinal Health, SEP 27, 2022, View Source [SID1234621453]). The company will webcast a discussion of these results beginning at 8:30 a.m. Eastern.

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To access the webcast and corresponding slide presentation, visit Cardinal Health’s Investor Relations page. No access code is required. Presentation slides and a webcast replay will be available until November 3, 2023.

On September 27, 2022 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a pre-commercial-stage biopharmaceutical company focused on oncology, reported its U.S. commercialization plan for APHEXDA (Motixafortide) in stem cell mobilization for autologous bone marrow transplantation for multiple myeloma patients (Press release, BioLineRx, SEP 27, 2022, View Source [SID1234621452]). If approved, the Company intends to commercialize APHEXDA in the U.S. independently in order to accelerate its availability to patients and to maximize the value of this innovative therapeutic candidate. To lead its U.S. operations and drive commercial strategy, the Company has appointed commercial product veteran Holly May to the role of President, BioLineRx USA.

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In the U.S., autologous stem cell transplants for patients with multiple myeloma and other conditions are highly concentrated within academic and regional centers. To support a robust commercial launch, the Company will employ a small and targeted sales force to support outreach to this well-defined community.

"We are excited to announce our plan to commercialize Motixafortide, now known by its FDA approved trade name APHEXDA, independently in the U.S., assuming FDA approval next year," said Philip Serlin, Chief Executive Officer of BioLineRx. "Our approach ensures focused outreach to transplant centers and enhanced value for the Company over other potential commercialization approaches examined. Since the beginning of 2022, we have been advancing key pre-launch activities. Our progress, together with our recent financings, puts us in an ideal position to efficiently build the additional infrastructure and targeted sales team to ensure the rapid uptake of APHEXDA."

"Our independent market research suggests that the U.S. market for mobilization agents used in stem cell transplants is approximately $360 million annually and growing," said Holly May, President, BioLineRx USA. "Given the totality of clinical and pharmacoeconomic data that we have compiled to date, we believe APHEXDA, if approved, can quickly become part of a new standard of care, allowing us to capture a significant share of this opportunity. Our U.S. commercial team is actively engaged in launch preparedness and excited about the potential of bringing this important therapeutic candidate to patients."

The Company recently announced that it submitted its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Motixafortide in stem cell mobilization for autologous bone marrow transplantation for multiple myeloma patients.

The NDA submission is based on the overwhelmingly positive top-line results from BioLineRx’s GENESIS Phase 3 trial of Motixafortide on top of G-CSF (versus placebo on top of G-CSF) in stem cell mobilization for autologous bone marrow transplantation in multiple myeloma patients. The study met all primary and secondary endpoints with a very high degree of statistical significance (p<0.0001). The combination was also found to be safe and well tolerated.

Investor and Key Opinion Leader Webinar
BioLineRx will provide more detail around its U.S. launch plans during an Investor and Key Opinion Leader Webinar that is occurring tomorrow, Wednesday, September 28, at 9:00 a.m. EDT.

The webinar will feature a presentation by Dr. John F. DiPersio, Chief of the Division of Oncology, Washington University School of Medicine, St. Louis, and lead investigator of BioLineRx’s GENESIS Phase 3 clinical study (the basis for the Company’s recently submitted New Drug Application), who will highlight the unmet need and current treatment landscape for the mobilization of stem cells (SCM) for multiple myeloma patients undergoing autologous stem cell transplantation.

Following Dr. DiPersio’s presentation, Lissa Gray, RN, who heads BioLineRx’s patient advocacy program, will moderate a panel discussion between an apheresis nurse, a multiple myeloma patient who underwent apheresis, and her caretaker, to provide a detailed assessment of the current treatment experience.

Holly May, President of BioLineRx USA, will then provide insight into the SCM market opportunity, as well as expand upon the Company’s plans to commercialize APHEXDA independently in the U.S., if approved.

Interested parties may register for the webinar here.

A replay of the webinar will be available on the Company’s Investor Relations page approximately two hours after the event’s completion. The webinar replay will be available until October 31, 2022.

About the GENESIS Trial
The GENESIS trial (NCT03246529) was initiated in December 2017. GENESIS was a randomized, placebo-controlled, multicenter study, evaluating the safety, tolerability and efficacy of Motixafortide and G-CSF, compared to placebo and G-CSF, for the mobilization of hematopoietic stem-cells for autologous transplantation in multiple myeloma patients. The primary objective of the study was to demonstrate that only one dose of Motixafortide on top of G-CSF is superior to G-CSF alone in the ability to mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. A key secondary objective of the study was to demonstrate that only one dose of Motixafortide on top of G-CSF is superior to G-CSF alone in the ability to mobilize ≥ 6 million CD34+ cells in only one apheresis session. In this regard, ~90% of patients in the GENESIS study went directly to transplantation after mobilizing the optimal number of stem cells following only one administration of Motixafortide on top of G-CSF and in only one apheresis session, compared to less than 10% of those receiving G-CSF alone. Additional objectives included time to engraftment of neutrophils and platelets and durability of engraftment, as well as other efficacy and safety parameters.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow with tumors. In 2022, it is estimated that more than 34,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.

About Autologous Stem Cell Transplantation
Autologous stem cell transplantation (ASCT) is part of the standard treatment paradigm for a number of blood cancers, including multiple myeloma. In the U.S., nearly 15,000 ASCTs are performed each year with the majority in patients with multiple myeloma. The current standard of care includes the administration of 5-8 daily doses of granulocyte colony stimulating factor (G-CSF), with or without 1-4 doses of plerixafor, and the performance of 1-4 apheresis sessions. For patients unable to mobilize sufficient numbers of cells for harvesting during this primary mobilization phase, rescue therapy is carried out, consisting of 1-4 additional doses of plerixafor on top of G-CSF, and the performance of an additional number of apheresis sessions as necessary. In light of this, an agent with superior mobilization activity may significantly reduce the mobilization and harvesting burden and associated risks of the ASCT process and lead to significant clinical and resource benefits.

On September 27, 2022 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare tumors and aggressive cancers reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for AL102 for the treatment of progressing desmoid tumors. AL102 is a potent, selective, oral gamma-secretase inhibitor (Press release, Ayala Pharmaceuticals, SEP 27, 2022, View Source [SID1234621451]).

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"We are pleased to receive FDA Fast Track designation for AL102 in progressing desmoid tumors, which we believe reinforces the large unmet medical need for patients with this serious disease. This designation holds important advantages that may expedite the development and regulatory review of AL102," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "We are very encouraged by the emerging body of clinical data supporting AL102 and, if approved, believe that this product could have a meaningful impact on patients’ lives."

The FDA grants Fast Track designation to facilitate development and expedite the review of therapies with the potential to treat a serious condition where there is an unmet medical need. A therapeutic that receives Fast Track designation can benefit from early and frequent communication with the agency, in addition to a rolling submission of the marketing application, with potential pathways for expedited approval that have the objective of getting important new therapies to patients more quickly.

AL102 is being evaluated in the ongoing RINGSIDE pivotal Phase 2/3 clinical trial in desmoid tumors. Positive interim results from Part A, the Phase 2 segment of this study, were presented at ESMO (Free ESMO Whitepaper) 2022, showing efficacy across all cohorts, with early tumor responses that deepened over time. AL102 was well tolerated. The company has initiated Part B of RINGSIDE (Phase 3), and is enrolling patients in an open label extension study.

About the RINGSIDE study
The RINGSIDE pivotal Phase 2/3 study is a randomized global multi-center trial. Part A of the study is evaluating the efficacy, safety, tolerability, and tumor volume by MRI after 16 weeks of AL102 in patients with desmoid tumors. It enrolled 42 patients and is evaluating 3 doses of AL102. Patients who participated in Part A are eligible to enroll into an open-label extension study at the Part B selected dose of 1.2 mg daily, and long-term efficacy and safety will be monitored.

Part B of the study, the Phase 3 segment, has been initiated. This is a double-blind, placebo-controlled segment enrolling up to 156 patients with progressive disease, comparing AL102 at 1.2 mg once daily to placebo. The primary endpoint for Part B is progression-free survival (PFS) with secondary endpoints including objective response rate (ORR), duration of response (DOR), tumor volume reduction, and patient-reported Quality of Life (QOL) measures. For more information on the RINGSIDE Phase 2/3 study with AL102 for the treatment of desmoid tumors, please visit ClinicalTrials.gov and reference Identifier NCT04871282 (RINGSIDE).

About Desmoid Tumors
Desmoid tumors also called aggressive fibromatosis or desmoid-type fibromatosis, are rare connective tissue tumors that typically arise in the upper and lower extremities, abdominal wall, head and neck area, mesenteric root, and chest wall with the potential to arise in additional parts of the body. Desmoid tumors do not metastasize, but often aggressively infiltrate neurovascular structures and vital organs. People living with desmoid tumors are often limited in their daily life due to chronic pain, functional deficits, general decrease in their quality of life and organ dysfunction. Desmoid tumors have an annual incidence of approximately 1,700 patients in the United States and typically occur in patients between the ages of 15 and 60 years. They are most commonly diagnosed in young adults between 30-40 years of age and are more prevalent in females. Today, surgery is no longer regarded as the cornerstone treatment of desmoid tumors due to a high rate of recurrence post-surgery and there are currently no FDA-approved systemic therapies for the treatment of unresectable, recurrent or progressive desmoid tumors.