On December 9, 2023 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported the presentation of data from a comprehensive safety review of patients treated in the Phase 1 ALPHA/ALPHA2 trials with ALLO-501/501A at the 65th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, CA (Press release, Allogene, DEC 9, 2023, View Source [SID1234638317]).

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The safety review, which encompasses all 87 Phase 1 patients treated in both relapsed/refractory (r/r) Large B Cell Lymphoma (LBCL) and follicular lymphoma (FL), demonstrates that investigational ALLO-647 added to standard lymphodepletion can safely provide a window for the expansion and persistence of AlloCAR T cells, and has the potential to induce deep and durable remissions in relapsed and treatment-refractory cancers.

"We believe in the immense potential of off-the-shelf CAR T products to not only address the limitations of current autologous CAR T cell therapy, but to also provide greater access to patients in need," said Zachary Roberts, M.D., Ph.D., Executive Vice President of Research & Development and Chief Medical Officer of Allogene. "We fully understand the importance of lymphodepletion to achieving optimal outcomes, and ALLO-647 is just the first generation of our innovative approaches to enhancing lymphodepletion to promote expansion of CAR T cells."

The inclusion of our ALLO-647 candidate in the lymphodepletion regimen is designed to selectively prevent host rejection of allogeneic CAR T cell products. As previously presented in the Phase 1 ALPHA/ALPHA2 studies1, CAR T cell-naive patients with r/r LBCL were able to obtain a durable response, including a complete remission rate of 42% and a median duration of response of 23.1 months.

In the studies, lymphodepletion consisted of three daily doses of fludarabine 30 mg/m2 and cyclophosphamide 300-500 mg/m2 (FC) and 39, 60, or 90 mg of ALLO-647 in divided doses prior to ALLO-501/501A infusion. The addition of ALLO-647 to standard lymphodepletion did not result in adverse events beyond those commonly observed with autologous CAR T cell therapy.

No unexpected safety concerns were observed. Neutropenia and anemia were the most common any-grade treatment-emergent adverse events (or TEAEs) and neutropenia, anemia, and thrombocytopenia were the most common Grade 3 or higher TEAEs. Grade 3 or higher cytopenias decreased over time from Day 28 to Month 4 and were consistent across all subsets of patients. Incidence of Grade 3 or higher cytopenias were consistent with that reported for autologous CAR T cell therapy.2-4

Safety: TEAEs of Special Interest

TEAEs, n (%)
All (N=87)
LBCL FL (n=26)
All LBCL
(n=61) CAR T Cell–Naive Pts Who Received
ALLO-501/501A Manufactured With
The Phase 2 Selected Process (n=33)
Any Grade Grade ≥3 Any Grade Grade ≥3 Any Grade Grade ≥3 Any Grade Grade ≥3
CRS 21 (24) 1 (1) 17 (28) 1 (2) 8 (24) 0 4 (15) 0
ICANS 1 (1) 0 1 (2) 0 0 0 0 0
Neurotoxicity 24 (28) 3 (3) 19 (31) 3 (5) 13 (39) 2 (6) 5 (19) 0
GvHD 0 0 0 0 0 0 0 0
IRR 48 (55) 5 (6) 31 (51) 4 (7) 16 (48) 3 (9) 17(65) 1 (4)
Infections 50 (57) 18 (21) 34 (56) 13 (21) 19 (58) 5 (15) 16 (62) 5 (19)

There were no reports of graft-versus-host disease (GvHD) or Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS). In total, 24% of patients experienced low-grade CRS, and there was 1 Grade 3 CRS event. Infection events were primarily low grade and manageable, with the most common being cytomegalovirus reactivation with an any-grade incidence of 25% and a Grade 3 or higher incidence of 9%. Incidence of infections were consistent with that reported for autologous therapy following lymphodepletion (12%-33% percent of patients).3-5 Eight patients experienced fatal adverse events not related to study treatment.

The EXPAND trial, currently enrolling in the United States and Europe, is expected to support licensure of ALLO-647, used in conjunction with standard low-dose FC lymphodepletion regimens. The trial will enroll approximately 70 patients with r/r LBCL who will be randomized to lymphodepletion with FCA90 (which includes 90 mg of ALLO-647) versus FC alone before receiving a single 120 million cell dose of ALLO-501A. The primary endpoint of the study is progression free survival (PFS).

Separately, the Company announced that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation (FTD) for the investigation of ALLO-647 in adult patients with r/r LBCL based on its potential to enhance standard lymphodepletion. FTD designation is intended to accelerate the development and review of treatments for serious and life-threatening diseases where no treatment exists or where the treatment in discovery may be better than what is currently available. ALLO-647 is investigated as a lymphodepleting agent in combination with flu/cy prior to infusion of allogeneic CD19-directed CAR T cells with genomes edited to knock out CD52.

About ALLO-501 and ALLO-501A
ALLO-501 and ALLO-501A are anti-CD19 AlloCAR TTM investigational products for the treatment of large B cell lymphoma. ALLO-501A, a next-generation anti-CD19 AlloCAR TTM product, eliminates the rituximab recognition domains in ALLO-501, which could allow for use in a broader patient population, including NHL patients with recent rituximab exposure. This product candidate is currently being studied in an ongoing potentially pivotal Phase 2 trial. In June 2022, the U.S. Food and Drug Administration granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-501A in r/r LBCL.

On December 8, 2023 Halia Therapeutics reported to start a Phase II trial of its pipeline candidate HT-6184 in myelodysplastic syndrome (MDS) early next year (Press release, Halia Therapeutics, DEC 8, 2023, View Source [SID1234638565]).

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CEO Dr Dave Bearss told the Clinical Trials Arena that the US-based company will be testing the candidate in MDS patients for the first time, with the first dosing due to take place in the US.

HT-6184 targets the protein NEK7 by blocking its ability to bind to NLRP3, which reduces the inflammatory response. The activation of NLRP3 drives the onset and progression of various conditions, including neurological and rheumatological diseases.

Phase II trial plans
The Phase II trial will measure endpoints including the level of creation of white and red blood cells. Patients will also be evaluated with a bone marrow biopsy.

The trial will enrol around 50 patients with MDS who are or are on the borderline of being transfusion-dependent.

Investigators will be looking for improvement in haemoglobin and whether there is improvement in transfusion dependency, with Bearss adding that the goal would be for patients to no longer be dependent, which he described as a meaningful endpoint. The planned trial is taking place internationally with screening for eligible patients ongoing. Site selection and initiation will take place in the US before the company expands to multiple countries, with plans for parts of Asia and Europe.

On December 8, 2023 ImmunoPrecise Antibodies Ltd. ("ImmunoPrecise" or "IPA" or the "Company"), reported the closing of its $1.265 million underwritten public offering of 1,265,000 common shares, including 165,000 common shares issued pursuant to the full exercise by the underwriter of its over-allotment option (Press release, ImmunoPrecise Antibodies, DEC 8, 2023, View Source [SID1234638399]). The public offering price for each common share, before the underwriter’s discount and commissions, was $1.00. All of the securities in the underwritten public offering were sold by the Company.

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The Company intends to use the net proceeds from the proposed offering for research and development; capital expenditures, including expansion of existing laboratory facilities; and working capital and general corporate purposes.

The Benchmark Company acted as the sole Book-Running Manager and R.F. Lafferty acted as Co-Manager for the offering.

Dorsey & Whitney LLP and Norton Rose Fulbright Canada LLP served as US and Canadian legal counsel, respectively, to the Company. Sheppard, Mullin, Richter & Hampton LLP served as legal counsel to The Benchmark Company, LLC.

The securities were offered and sold pursuant to a shelf Registration Statement on Form F-3 (File No. 333-273197) that was declared effective by the United States Securities and Exchange Commission (the "SEC") on July 14, 2023. A copy of the final prospectus supplement and accompanying prospectus describing the terms of the offering has been filed with the SEC and are available on its website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may also be obtained by contacting The Benchmark Company, LLC, 150 East 58th St., 17th Floor, New York, NY 10155, by telephone at 212-312-6700 or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in Canada or any other state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 8, 2023 Pfizer Inc. (NYSE:PFE) reported the European Commission (EC) has granted conditional marketing authorization for ELREXFIO (elranatamab). ELREFXIO is a targeted immunotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy (Press release, Pfizer, DEC 8, 2023, View Source [SID1234638356]). ELREXFIO is an off-the-shelf (ready-to-use) B-cell maturation antigen (BCMA)-CD3-directed bispecific antibody (BsAb) immunotherapy that induces deep and durable responses, with a manageable tolerability profile as well as convenient subcutaneous dosing.

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"More than 50,000 Europeans are diagnosed with multiple myeloma each year, and too often, they face relapse and treatment resistance," said Chris Boshoff, Chief Oncology Research and Development Officer and Executive Vice President, Pfizer. "Today’s approval provides a new, broadly available option for people with hard-to-treat multiple myeloma, and we continue to explore the use of ELREXFIO in earlier lines of treatment so that more people may ultimately benefit from this therapy."

The conditional marketing authorization for ELREXFIO is valid in all 27 EU member states as well as Iceland, Liechtenstein, and Norway. This authorization follows the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) recommendation for a conditional marketing authorization on October 12, 2023.

Authorization was based on data from cohort A of the Phase 2 MagnetisMM-3 study (NCT04649359) showing meaningful responses among heavily pretreated RRMM patients – at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody – who received ELREXFIO as their first BCMA-directed therapy. In an analysis of these patients (n=123), the objective response rate was 61%, with a 71% probability of maintaining a response at 15 months.

The results from MagnetisMM-3 also established once-every-other-week dosing with ELREXFIO for all responding patients after 24 weeks of weekly therapy, which means less time at the clinic and potentially greater long-term treatment tolerability. Among responding patients who switched to every-other-week dosing at least six months prior to the data cut-off date (n=50), 80% maintained or improved their response after the switch, with 38% attaining a complete response (CR) or better after the switch. These data were published in Nature Medicine.

The most common adverse reactions to ELREXFIO are cytokine release syndrome (CRS) (58%), anemia (54%), neutropenia (45%), fatigue (44%), upper respiratory tract infection (39%), injection site reaction (38%), diarrhea (38%), pneumonia (37%), thrombocytopenia (36%), lymphopenia (30%), decreased appetite (27%), rash (26%), joint pain (arthralgia) (25%), fever (pyrexia) (27%), hypokalemia (23%), nausea (21%), and dry skin (21%). Serious adverse reactions are pneumonia (31%), sepsis (15%), CRS (13%), anemia (6%), upper respiratory tract infection (5%), urinary tract infection (3%), febrile neutropenia (3%), dyspnea (2%), and pyrexia (2%). Most cases of CRS were Grade 1 (44% of patients), with Grade 2 in 14% and Grade 3 in less than 1% of patients.

Due to the risk of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), patients should be monitored for signs and symptoms for 48 hours after administration of each of the two step-up doses within the ELREXFIO dosing schedule and instructed to remain in proximity of a healthcare facility. In the EU, precautionary hospitalization is not required. Patients are not required to stay near a healthcare facility for the 76-mg first treatment dose.

About Multiple Myeloma

Multiple myeloma (MM) is an aggressive and currently incurable blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection.1 MM is the second most common type of blood cancer, with over 50,000 new cases diagnosed annually in Europe and 176,000 new cases diagnosed globally each year.2,3 About 40% of those diagnosed with MM won’t survive beyond five years,4 and most will receive four or more lines of therapy due to relapse.5 While disease trajectory varies for each person, relapses are nearly inevitable.6 The goal of therapy for people with RRMM is to achieve disease control with acceptable toxicity and improved quality of life.7

About ELREXFIO (elranatamab)

ELREXFIO is a subcutaneously delivered B-cell maturation antigen (BCMA)-CD3-directed bispecific antibody (BsAb) immunotherapy that binds to BCMA on myeloma cells and CD3 on T-cells, activating the T-cells to kill myeloma cells.

In August 2023, ELREXFIO was approved by the U.S. Food and Drug Administration (FDA) under its Accelerated Approval Program, which allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need. ELREXFIO has also received approval in Switzerland and Brazil under Project Orbis, a framework for the concurrent submission and review of oncology drugs among international partners to potentially expedite approvals. Three other countries (Canada, Australia, and Singapore) are participating in Project Orbis. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has granted ELREXFIO Innovative Medicine Designation and the Innovation Passport for the treatment of MM.

Pfizer’s extensive MagnetisMM clinical development program is continuing to investigate ELREXFIO’s use across the entire spectrum of patients with MM, from RRMM to newly diagnosed MM. Ongoing registrational-intent trials are exploring ELREXFIO both as monotherapy and in combination with standard or novel therapies. These include MagnetisMM-5 in the double-class exposed setting, MagnetisMM-6 in newly diagnosed patients who are ineligible for stem cell transplant, and MagnetisMM-7 in newly diagnosed patients after transplant.

Detailed information on this medicinal product is available on the website of the European Medicines Agency View Source

U.S. INDICATION

ELREXFIO may cause side effects that are serious, life-threatening, or can lead to death, including cytokine release syndrome (CRS) and neurologic problems. CRS is common during treatment with ELREXFIO.

Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS or neurologic problems, including:

fever of 100.4°F (38°C) or higher
trouble breathing
chills
dizziness or light-headedness
fast heartbeat
headache
increased liver enzymes in your blood
agitation, trouble staying awake, confusion or disorientation, or seeing or hearing things that are not real (hallucinations)
trouble speaking, thinking, remembering things, paying attention, or understanding things
problems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasms
numbness and tingling (feeling like "pins and needles")
burning, throbbing, or stabbing pain
changes in your handwriting
Due to the risk of CRS, you will receive ELREXFIO on a "step-up" dosing schedule and should be hospitalized for 48 hours after the first "step-up" dose and for 24 hours after the second "step-up" dose of ELREXFIO.

For your first dose, you will receive a smaller "step-up" dose of ELREXFIO on day 1
For your second dose, you will receive a larger "step-up" dose of ELREXFIO, which is usually given on day 4 of treatment
For your third dose, you will receive the first "treatment" dose of ELREXFIO, which is usually given on day 8
If your dose of ELREXFIO is delayed for any reason, you may need to repeat step-up dosing. Before each dose of ELREXFIO you receive during the step-up dosing schedule, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses.

ELREXFIO is available only through the ELREXFIO Risk Evaluation and Mitigation Strategy (REMS) Program due to the risk of CRS and neurologic problems. You will receive an ELREXFIO Patient Wallet Card from your healthcare provider. Carry the ELREXFIO Patient Wallet Card with you at all times and show it to all of your healthcare providers. The ELREXFIO Patient Wallet Card lists signs and symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the signs and symptoms listed on the ELREXFIO Patient Wallet Card. You may need to be treated in a hospital.

Before taking ELREXFIO, tell your healthcare provider about all of your medical conditions, including if you:

have an infection
are pregnant or plan to become pregnant. ELREXFIO may harm your unborn baby. Females who are able to become pregnant should do a pregnancy test before starting treatment with ELREXFIO and should use effective birth control during treatment and for 4 months after your last dose of ELREXFIO. Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with ELREXFIO
are breastfeeding or plan to breastfeed. It is not known if ELREXFIO passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose of ELREXFIO
Tell your healthcare provider about all of the medications you take, including prescription and over-the-counter medications, vitamins, and herbal supplements.

Do not drive, operate heavy or potentially dangerous machinery, or do other dangerous activities during treatment with ELREXFIO:

for 48 hours after completing each of the 2 doses of ELREXFIO that are part of the "step-up dosing schedule" and your first full treatment dose, and
at any time during treatment with ELREXFIO if you develop any new neurologic symptoms, such as dizziness, confusion, shaking (tremors), sleepiness, or any other symptom that impairs consciousness, until the symptoms go away.
Infections: Upper respiratory tract infection and pneumonia are common during treatment with ELREXFIO. ELREXFIO can cause bacterial and viral infections that are severe, life-threatening, or that may lead to death.

Your healthcare provider may prescribe medications for you to help prevent infections and treat you as needed if you develop an infection during treatment with ELREXFIO
Tell your healthcare provider right away if you develop any signs or symptoms of an infection during treatment with ELREXFIO, including: fever of 100.4°F (38°C) or higher, chills, cough, shortness of breath, chest pain, sore throat, pain during urination, or feeling weak or generally unwell
People with active infections should not start ELREXFIO
Decreased white blood cell counts: Decreased white blood cell counts are common during treatment with ELREXFIO and can also be severe. A fever can occur with low white blood cell counts and may be a sign that you have an infection. Your healthcare provider will treat you as needed.

Liver problems: ELREXFIO can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Tell your healthcare provider if you develop any of the following signs or symptoms of a liver problem, including:

tiredness
loss of appetite
pain in your right upper stomach-area
dark urine
yellowing of your skin or the white part of your eyes
The most common side effects of ELREXFIO include:

tiredness
injection site reaction, such as redness, itching, pain, bruising, rash, swelling, and tenderness
diarrhea
muscle and bone pain
decreased appetite
rash
cough
nausea
fever
The most common severe abnormal lab test results with ELREXFIO include decreased white blood cells, red blood cells, and platelets.

Your healthcare provider may temporarily or permanently stop ELREXFIO if you have any of the side effects listed and they are severe. These are not all of the possible side effects of ELREXFIO.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is ELREXFIO?

ELREXFIO is a prescription medication used to treat adults with multiple myeloma who:

have already received at least 4 treatment regimens, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, to treat their multiple myeloma, and
their cancer has come back or did not respond to prior treatment.
ELREXFIO was approved based on patient responses and durability of response. There are ongoing studies to confirm its clinical benefit. It is not known if ELREXFIO is safe and effective in children.

Please read full Prescribing Information, including BOXED WARNING, for ELREXFIO.

On December 8, 2023 NiKang Therapeutics Inc. ("NiKang"), a clinical stage biotech company focused on developing innovative small molecule oncology medicines to help patients with unmet medical needs, reported that it has entered into a clinical trial collaboration and supply agreement with F. Hoffmann-La Roche Ltd. ("Roche") to evaluate NKT2152, a small molecule that inhibits hypoxia inducible factor 2α (HIF2α), in combination with standard-of-care atezolizumab (Tecentriq) and bevacizumab (Avastin) in first-line treatment of unresectable/advanced hepatocellular carcinoma (HCC) (Press release, NiKang Therapeutics, DEC 8, 2023, View Source [SID1234638355]). This collaboration will utilize Roche’s MORPHEUS-LIVER phase 1b/2 platform for rapid and efficient combination development.

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This randomized multi-regional phase 1b/2 trial is intended to evaluate the efficacy and safety of NKT2152 in combination with atezolizumab and bevacizumab versus atezolizumab and bevacizumab in patients with unresectable/advanced HCC not previously treated with systemic therapy. Patient enrollment will begin in 2024. Under the collaboration, Roche will sponsor the study, and each company will supply its respective anti-cancer agent to support the trial. NiKang retains its development and commercialization rights of NKT2152. Additional financial details of the agreement were not disclosed.

"We are thrilled to enter this collaboration with Roche, which allows us to explore the broader potential of our HIF2α inhibitor NKT2152 in treating solid tumors beyond clear cell Renal Cell Carcinoma (ccRCC)," said Zhenhai Gao, Ph.D., co-founder, president, and CEO of NiKang. "Based on the compelling scientific rationale and supporting preclinical studies, we have a keen interest in assessing NKT2152 in HCC patients. This collaboration enables us to leverage Roche’s MORPHEUS-LIVER phase 1b/2 platform to explore this promising opportunity expeditiously."

NKT2152 is currently in a phase 1/2 dose escalation and expansion trial (NCT05119335) that is designed to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity in patients with advanced ccRCC.