On December 21, 2023 Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported that a Marketing Authorization Application (MAA) was submitted yesterday to the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK for DCVax-L for glioblastoma brain cancer (Press release, Northwest Biotherapeutics, DEC 21, 2023, View Source [SID1234638751]).

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The MAA seeks approval for commercialization of DCVax-L for both newly diagnosed and recurrent glioblastoma (GBM). The application also requests to be considered under the MHRA’s rapid 150-day review pathway, which the agency has established for new medicines for serious unmet medical needs.

"We are very excited to reach this important milestone as the culmination of more than 20 years of research and clinical development," commented Linda Powers, Company CEO. "We are extremely grateful to all of the parties who have made this possible, including the patients, the investigators and the shareholders whose patience and support have been invaluable. We believe DCVax-L can offer a much needed new treatment option for GBM patients, both alone and in combination with other treatment agents. We look forward to bringing the treatment to as many patients as possible, including in community settings where most patients are treated."

GBM is the most lethal and most common form of primary brain cancer. Despite well over 400 clinical trials of a wide range of treatment agents, patient survival in newly diagnosed GBM is only 15-17 months and has not meaningfully improved in 20 years; survival in recurrent GBM is only 6-8 months and has not improved in 30 years.

The Company’s international Phase III trial demonstrated a statistically significant and clinically meaningful extension of median survival in both newly diagnosed and recurrent GBM in patients treated with DCVax-L compared with independently selected, matched, contemporaneous, pre-specified external controls. The trial also demonstrated more than doubling of the percentage of patients alive at 5 years in newly diagnosed GBM, and more than doubling of patients alive at 3 years after tumor recurrence in recurrent GBM patients, although the numbers of patients available for comparison at late time points was small, especially in the external control populations.

One of the key factors making GBM so difficult to treat is that it is an extremely heterogeneous tumor. "Accumulating evidence suggests that intratumor heterogeneity likely is the key to understanding treatment failure" in GBM (Sottoriva, PNAS, 2013). Another key challenge is that as GBM develops, it induces an immunosuppressive microenvironment which compounds the difficulty of mounting an effective immune response against the tumor – especially within the central nervous system, which is an immune privileged space behind the blood brain barrier.
DCVax-L is designed to address both of these key challenges.

As the Company previously reported, proteomic studies have demonstrated that a single tumor lysate sample contained tens of thousands of different peptides and, out of this pool, the dendritic cells selected, processed and presented over 600 different peptides (tumor targets) to T cells. T cell studies (TCR sequencing and T cell clonal expansion assays) analyzing the breadth and strength of T cell response following DCVax-L treatment have found extensive responses, including clonal expansion of up to 800 T cell clones at month 4 and up to 1200 T cell clones at month 8 in the samples studied. Each T cell clone focuses on a particular and distinct target. In individuals not being treated with the vaccine, only 2 – 20 new T cells clones are seen between month 4 and month 8.

The results of these proteomic, T cell and other studies provide support for what the Company believes to be the mechanism of action of DCVax-L: i.e., mobilizing a broad spectrum and strong de novo T cell response that addresses the extensive heterogeneity of GBM and overcomes the immunosuppressive microenvironment around the tumor.

The Company believes that this mechanism of action will be applicable for most types of solid tumors. Solid tumors comprise approximately 90% of all cancers, and a key difficulty that other treatment approaches have encountered with solid tumors is their heterogeneity.

The Company has already had positive results with DCVax-L in some compassionate use cases with other diverse solid tumors. The Company looks forward to building on its experience with DCVax-L in GBM and the compassionate use cases to address a wide range of other operable solid tumors.

The Company also had positive results in its Phase 1 trial of DCVax-Direct, in which more than a dozen diverse types of inoperable solid tumors were treated. DCVax-Direct involves essentially the same mechanism of action as DCVax-L, except that the tumor target proteins are taken up by the dendritic cells in situ in the tumor following intra-tumoral injection, rather than from tumor lysate from a surgically resected tumor tissue sample. The Company looks forward to resuming its clinical development of DCVax-Direct for a wide range of inoperable solid tumors.

For the GBM MAA, the Company anticipates that the review process will be a period of intensive and extensive further work involving responding to questions and requests for further information by the regulatory authority as well as preparing for and undergoing detailed inspections of the contract research organizations (CROs) that managed the trial, the Sponsor, the Trial Master File, a number of individual trial sites selected by the regulator from among the 94 sites that participated in the trial, the GMP facility and manufacturing information.

On December 21, 2023 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported that Gilead Sciences (‘Gilead’) has purchased 15 million shares of HOOKIPA’s common stock for approximately $21.25 million, at a price of $1.4167 per share (Press release, Hookipa Biotech, DEC 21, 2023, View Source [SID1234638750]).

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In addition, HOOKIPA has the right, subject to certain terms and conditions, to sell an additional approximately $8.75 million of common stock to Gilead as pro-rata participation in potential future equity raises. The agreement with Gilead replaces the stock purchase agreement that Hookipa entered into with Gilead in 2022.

"We have a tremendous partnership with Gilead, who have been incredible believers in our arenavirus platform since our initial collaboration and license agreement began more than five years ago," said Joern Aldag, Chief Executive Officer at HOOKIPA. "Together, we have made meaningful progress to find a potential functional cure for HIV. Most recently, we received clearance from the U.S. Food and Drug Administration of our Investigational New Drug application for HB-500 and are excited to begin our Phase 1 trial in the first half of next year. We are excited to continue our relationship with Gilead, and we are collectively optimistic about the potential of our partnership to benefit patients."

The transaction closed on December 20, 2023. Following the completion of the stock purchase, Gilead’s ownership in HOOKIPA increased to 18,759,465 shares, or approximately 19.4% of HOOKIPA’s outstanding shares of Common Stock.

HB-500 is an alternating, 2-vector arenaviral therapeutic vaccine that is being evaluated as part of a potential curative regimen for HIV. One vector is based on lymphocytic choriomeningitis virus (LCMV) as its arenaviral backbone; another vector is based on Pichinde virus (PICV). Both encode the same HIV antigens. The alternating 2-vector approach is designed to further focus the immune response against the target antigen.

HB-500 is one of two separate development programs in HOOKIPA’s collaboration and license agreement with Gilead. HOOKIPA is responsible for advancing the HIV program through the completion of a Phase 1b clinical trial. Gilead has the exclusive right to assume further development of the program thereafter.

For further details, refer to the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission (the ‘SEC’) on December 21, 2023.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. Any offering of the shares of common stock described above under the resale registration statement will only be by means of a prospectus.

On December 21, 2023 Galecto, Inc. (the "Company," or "Galecto") reported positive topline results from its Phase 2a MYLOX-1 trial of GB2064 for the treatment of myelofibrosis (Press release, Galecto Biotech, DEC 21, 2023, View Source [SID1234638749]). The MYLOX-1 trial dosed a total of 18 myelofibrosis patients, of which 11 (61%) patients had previously received janus kinase inhibitor ("JAKi") therapy with ruxolitinib, with eight of those patients being refractory and three being intolerant to JAKi therapy. Six out of ten evaluable myelofibrosis patients who received GB2064 monotherapy for at least six months experienced a ≥ 1-grade reduction in collagen fibrosis of the bone marrow, an improvement suggesting that GB2064 could impact the progression of the disease and be disease-modifying.

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Fibrosis is a key disease mechanism of myelofibrosis that destroys bone marrow function. Reducing fibrosis is required to slow the progression of the disease. Bone marrow biopsies taken during the study showed that GB2064 penetrated the bone marrow and could exert its anti-fibrotic effect directly in the disease compartment. Furthermore, GB2064 demonstrated target engagement systemically by binding to lysyl oxidase-like 2 (LOXL2) in plasma.

All six patients who experienced a > 1-grade reduction in bone marrow fibrosis score also showed stable hematological parameters, including hemoglobin, white blood cell count and platelets. At six months of treatment, one patient obtained a ≥35% reduction in spleen volume, two patients reduced their Total Symptom Score (TSS) by more than 50% and one patient had an anemia response. Four of these patients have entered the extension phase of the study due to the clinical benefit derived from GB2064 as evaluated by the treating physician, with one patient receiving treatment for more than 30 months.

GB2064 showed a generally acceptable tolerability profile in the MYLOX-1 trial. Eighteen patients were dosed with GB2064 monotherapy in the MYLOX-1 trial. Eight patients completed treatment in the core phase of the MYLOX-1 trial and ten patients discontinued treatment due to an adverse event or disease progression. The most commonly observed treatment-related adverse events were gastrointestinal in nature and were manageable in most patients with standard therapy. The only treatment-related serious adverse event was a case of fall, which was assessed as possibly related to GB2064 by the investigator.

Galecto will not make any decisions relating to funding additional trials with GB2064 until it completes its previously announced strategic alternative process.

About the MYLOX-1 Trial

The MYLOX-1 trial was a Phase 2, open-label, single-arm study in myelofibrosis patients who were ineligible, refractory, or intolerant to JAKi therapy. These patients have a progressive disease with poor quality of life, high mortality rates and very limited treatment options. Patients received GB2064 orally at a dose of 1000mg twice daily for nine months and undergo bone marrow biopsies at the beginning of the trial and again at months 3, 6 and 9. The primary endpoint of the MYLOX-1 trial was to assess the safety and tolerability of GB2064.

Apart from evaluating the safety and tolerability of GB2064, key secondary objectives of the MYLOX-1 trial were to evaluate hematological parameters as well as the direct anti-fibrotic activity of GB2064 by blocking LOXL2 in an indication that allows for repeated tissue biopsies.

On December 21, 2023 Galapagos NV (Euronext & NASDAQ: GLPG) reported that the first patient has been dosed in PAPILIO-1, the Phase 1/2 study to evaluate the safety, efficacy, and feasibility of our seven-day vein-to-vein, point-of-care manufactured BCMA CAR-T candidate, GLPG5301, in adult patients with relapsed/refractory multiple myeloma (rrMM) (Press release, Galapagos, DEC 21, 2023, View Source [SID1234638748]). This is Galapagos’ third oncology CAR-T program in clinical development.

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GLPG5301 is an autologous, second-generation/4-1BB B-cell maturation antigen (BCMA)-directed CAR-T product candidate, administered as an intravenous infusion of a fresh product in a single fixed dose, at point-of-care.

"Patients living with relapsed/refractory multiple myeloma have a very poor prognosis and a significant high unmet medical need for novel treatment options. CAR-T therapy is one such option. By combining innovative science with breakthrough point-of-care delivery of novel CAR-T therapies, we aim to enhance patient outcomes and improve their quality of life," said Jeevan Shetty, Head of Clinical Development Oncology at Galapagos. "We are very pleased that the first patient with rrMM in PAPILIO-1 has been dosed with our BCMA CAR-T candidate, GLPG5301. This marks another milestone in the roll-out of our point-of-care network and the build-up of our CAR-T portfolio, which now consists of three ongoing clinical programs in severe hemato-oncology indications."

About the PAPILIO-1 Phase 1/2 study (EU CT 2022-500782-27-00)
PAPILIO-1 is a Phase 1/2, open-label, multi-center study to evaluate the feasibility, safety, and efficacy of point-of-care manufactured GLPG5301, our BCMA CAR-T product candidate, in patients with relapsed/refractory multiple myeloma (rrMM) after ≥2 prior lines therapy. The primary objective of the Phase 1 part of the PAPILIO-1 study is to evaluate safety and determine the recommended dose for the Phase 2 part of the study. The primary objective of the Phase 2 part of the study is to evaluate the efficacy of GLPG5301, as measured by the objective response rate (ORR). Secondary objectives for both Phase 1 and Phase 2 include further assessment of the safety of GLPG5301, additional efficacy endpoints, including assessment of minimal residual disease (MRD), as well as the feasibility of point-of-care manufacture of GLPG5301 in rrMM patients. Each enrolled patient will be followed for 24 months.

During Phase 1, up to 3 dose levels will be evaluated and at least 12 patients will be enrolled to establish the recommended Phase 2 dose. Approximately 30 additional patients will be enrolled in the Phase 2 part of the study to confirm the safety and efficacy of GLPG5301.

About Galapagos’ innovative approach to CAR-T manufacturing near the point-of-care
Galapagos’ decentralized, innovative point-of-care CAR-T manufacturing platform consists of an end-to-end xCellit workflow management and monitoring software system, a decentralized, functionally closed, automated manufacturing platform for cell therapies (using Lonza’s Cocoon) and a proprietary quality control (QC) testing and release strategy. The combination of these three core components offers the potential for administration of a fresh product, a median vein-to-vein time of 7 days (i.e. the time between T-cell collection and CAR-T infusion), and greater physicians oversight throughout the process.

About Relapsed/refractory multiple myeloma (rrMM)
Multiple myeloma (MM) is typically characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin. The plasma cells proliferate in the bone marrow and may result in extensive skeletal destruction with osteopenia, and osteolytic lesions with or without pathologic fractures. The diagnosis of MM is made when one (or more) of the following clinical presentations are present: bone pain with lytic lesions discovered on routine skeletal films or other imaging modalities, an increased total serum protein concentration with the presence of a monoclonal protein in the urine or serum, and anemia, hypercalcemia or renal failure. The patient may be either symptomatic or their disease may be discovered incidentally.

Despite improvements in treatment, patient with MM ultimately relapse or become refractory to available regiments. Triple-refractory (refractory to CD38 monoclonal antibodies [mAbs], proteasome inhibitor [PI] and immunomodulatory drug [IMiD] or penta-refractory (refractory to CD38 mAbs, 2 Pls and 2 IMiDs) patients have a poor prognosis and are in urgent need of novel treatment options.

On December 21, 2023 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated, localized biologics, reported that Sean McCarthy, D.Phil., president, chief executive officer, and chairman, will present at the 42nd Annual J.P. Morgan Healthcare Conference on Wednesday, January 10, 2024 at 5:15 p.m. PT (Press release, CytomX Therapeutics, DEC 21, 2023, View Source [SID1234638747]).

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A live webcast of the presentation will be available on the Events and Presentations page of CytomX’s website at www.cytomx.com. An archived replay will be available for 30 days following the event. In addition, management will be available for one-on-one meetings with investors who are registered to attend the conference.