On November 14, 2022 NexImmune, Inc. (Nasdaq: NEXI), a biotechnology company developing a novel approach to immunotherapy designed to orchestrate a targeted immune response by directing the function of antigen-specific T cells for liquid and solid malignancies, reported financial results for the third quarter of 2022 and announced a change in corporate strategy (Press release, NexImmune, NOV 14, 2022, View Source [SID1234624009]).

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"While we remain confident in the potential therapeutic benefit of our AIM ACT cell therapy programs, following a strategic review of our pipeline, indications, timelines and cash position, we have decided that the best path forward for NexImmune is to realign internal resources to focus on advancing our AIM INJ ‘off-the-shelf’ platform," said Kristi Jones, Chief Executive Officer. "We believe that the AIM INJ therapeutic modality offers the most disruptive potential to benefit patients, as well as the greatest potential to create long-term value for our shareholders. We believe there is a high level of excitement and momentum around our AIM INJ platform and its ‘off-the-shelf’ applications. Internally and externally generated evidence show encouraging signals of preclinical activity in models of oncology and autoimmune disorders. We will provide an update on these programs and continue to focus our resources to demonstrate the potential of our AIM INJ ‘IND engine’ to enable a rapid path to clinical development."
Jones continued, "Our AIM ACT cell therapy product candidates currently in clinical trials continue to show clinical activity in early dose escalation and are well-tolerated in patients. While we will be pausing our cell therapy clinical trials, we are exploring external opportunities with academic centers and corporate collaborators with the potential to continue advancing our clinical and preclinical programs. Importantly, we have demonstrated unique capabilities to successfully transfer our platform manufacturing process, rapidly validate targets and deliver IND-ready products in months. We will retain the internal expertise and core capabilities which will be fully leveraged, provide utility and drive value, regardless of modality."
Business and Strategy Update
The Company’s realignment of R&D resources to focus on the AIM INJ platform will extend its cash runway and enable greater focus on generating data and advancing the AIM INJ preclinical programs. The Company will pause development of its current adoptive cell therapy (AIM ACT) products in the NEXI-001 trial in relapsed refractory AML following hematopoietic stem cell transplantation (HSCT). The Company will not initiate the NEXI-003 trial in HPV-mediated tumors at this time and, as previously disclosed, the NEXI-002 trial in multiple myeloma will also remain paused. As part of this strategic realignment, the Company intends to:

AIM INJ, Injectable "Off-the-shelf" Antigen-Specific Immunotherapy, and Other Preclinical Research
•Maintain development capabilities and expand collaborations necessary to continue to generate data and information needed to advance preclinical programs to Investigational New Drug (IND) application submission.
•Continue multiple ongoing preclinical studies in oncology and autoimmune disorders and initiate several additional studies. Initial preclinical evidence demonstrates the potential to modify the course of autoimmune diseases using nanoparticles designed to treat and ultimately to induce tolerance.
NEXI-001 Relapsed Refractory AML Post Allo-HSCT
•Continue to dose and follow patients currently enrolled in the trial.
•Announce data for currently enrolled patients, which is expected in the first quarter of 2023.
NEXI-003 HPV-Related Cancers
•Explore opportunities to develop this adoptive cell therapy with external partners and collaborators and develop a corporate HPV strategy that utilizes the AIM INJ modality.
•Pause current ongoing activities required to initiate the NEXI-003 cell therapy trial and focus on developing a potential product candidate using the AIM INJ platform.
Operational Changes
•Implement a strategic realignment initiative, which is designed to reduce costs and reallocate resources towards our AIM INJ preclinical development programs. As part of this strategy, the Company will initiate a workforce reduction plan to reduce headcount by approximately 30%, primarily affecting the clinical development, manufacturing and administrative staff that had been needed to support the AIM ACT clinical programs.
•The Company estimates that it will incur approximately $0.7 million of costs in connection with the reduction in workforce related to severance pay and other related termination benefits and expects the majority of the costs associated with the restructuring to be incurred during the fourth quarter ending December 31, 2022.
Select Third Quarter 2022 Financial Highlights
Cash, cash equivalents, and marketable securities for the Company as of September 30, 2022 were $45.9 million compared to $53.1 million for the quarter ending June 30, 2022. Based on current operating plans, including the impact of the ongoing restructuring, NexImmune expects that its existing cash and cash equivalents will enable the Company to fund its operating and capital expenditure requirements through the third quarter of 2023.

Research and development expenses were $11.1 million in the third quarter of 2022, compared to $11.3 million for the same period in the prior year.

General and administrative expenses were $3.7 million, compared to $4.2 million for the same period in the prior year. The decrease was primarily due to decreased personnel-related expenses partially offset by increased professional fees.
Net loss, according to generally accepted accounting principles in the U.S. GAAP, was $14.7 million for the quarter, or a basic and diluted GAAP loss per share of $0.60. This compares to a net loss of $14.6 million, or a basic and diluted GAAP loss per share of $0.65, for the same period in the prior year.

On November 14, 2022 Neoleukin Therapeutics, Inc., "Neoleukin" (NASDAQ:NLTX), a biopharmaceutical company utilizing sophisticated computational methods to design de novo protein therapeutics, reported financial results for the third quarter ended September 30, 2022 as well as a strategic decision to discontinue development of NL-201, a fully de novo IL-2/IL-15 agonist, and focus on advancing next-generation de novo protein therapeutics based on Neoleukin’s expertise in designing and testing novel cytokine mimetics and experience with advanced machine learning (Press release, Neoleukin Therapeutics, NOV 14, 2022, View Source [SID1234624008]).

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"We will be using the information we have learned from the development of NL-201 and advances in protein design to build the next generation of de novo protein therapeutics," said Jonathan Drachman, M.D., Chief Executive Officer at Neoleukin. "We expect to focus on technology that widens the therapeutic window, such as the development of targeted and conditionally activated molecules to create potent immune agonists. We believe we are well positioned to do this work based on our expertise in de novo protein design combined with our experience in advanced machine learning and neural networks, which allows us to predict and create structures for de novo proteins with more sophisticated and dynamic structural elements than was previously possible."

"This coincides with a strategic decision to discontinue development of NL-201, which we believe was the first fully de novo protein to be evaluated in clinical trials," said Dr. Drachman. "We are grateful to the patients and families that participated in this Phase 1 trial and to the investigators and study personnel who enabled rapid testing of NL-201 during a global pandemic."

Discontinuation of NL-201 Development
Neoleukin announced today that it is discontinuing development of NL-201, its first de novo cytokine mimetic to be tested in patients. Preliminary monotherapy data from the Phase 1 study of NL-201 demonstrated engagement of the target receptor, expected pharmacodynamic changes for a potent IL-2/IL-15 agonist, and did not demonstrate significant immunogenicity even after multiple cycles of therapy—an important de-risking of the potential for de novo proteins that may be administered over many weeks and months. However, based on a review of the preliminary data, the expected benefit to risk ratio for patients, and recent developments in the field of IL-2 therapeutics, Neoleukin determined that the resources required to continue development would be better applied to advancing the next generation of de novo protein therapeutics.
Corporate Reorganization
As a result of the decision to discontinue development of NL-201, on November 12, 2022, Neoleukin’s Board of Directors approved a restructuring plan, including a reduction in force of approximately 40%. Cost savings as a result of this reduction in force as well as the discontinuation of development of NL-201 are expected to extend Neoleukin’s existing cash runway into the second half of 2025.
Summary of Financial Results
Cash Position: Cash, cash equivalents, and short-term investments totaled $106.9 million as of September 30, 2022, compared to $142.5 million as of December 31, 2021.
R&D Expenses: Research and development expenses for the third quarter of 2022 decreased to $9.5 million from $9.9 million for the third quarter of 2021. The decrease was primarily due to a decrease in personnel-related costs, partially offset by increases in costs related to the Phase 1 clinical trial of NL-201.
G&A Expenses: General and administrative expenses for the third quarter of 2022 decreased to $4.1 million from $5.6 million for the third quarter of 2021. The decrease was primarily attributable to decreases in personnel-related and facility-related costs.
Net Loss: Net loss for the third quarter of 2022 was $13.1 million compared to a net loss of $15.4 million in the third quarter of 2021.

On November 14, 2022 NANOBIOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported completion of the dose escalation part of a phase 1 dose escalation and dose expansion study evaluating potential first-in-class radioenhancer NBTXR3 for patients with locally advanced (LA) or borderline resectable (BR) pancreatic cancer (PC) (Press release, Nanobiotix, NOV 14, 2022, View Source [SID1234624006]). The phase 1 study ("Study 2019-1001") is being conducted by The University of Texas MD Anderson Cancer Center (MD Anderson).

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"The tolerable safety profile, establishment of recommended phase 2 dose, and early signals of efficacy we have observed in the dose escalation part for locally advanced patients of our phase 1 study give us confidence to now include borderline resectable patients in the expansion part," said Leonard A. Farber, MD, Chief Clinical and Medical Affairs Officer at Nanobiotix. "In the borderline resectable pancreatic cancer population, a positive correlation has been observed between achieving resectability through local and systemic control with preoperative therapy and potentially improving survival outcomes. Inclusion of the borderline resectable stage in the study will also expand the eligible patient population to include a larger proportion of pancreatic cancer patients, allowing for the robust evaluation of NBTXR3’s potential to have a significant impact in this recalcitrant disease."

Study 2019-1001 is being conducted as part of the ongoing strategic collaboration between Nanobiotix and MD Anderson. The complete dose escalation part of the study recruited 11 patients, and all patients had unresectable disease at study entry. A single intratumoral injection of NBTXR3 followed by 15 fractions of RT showed to be feasible and well-tolerated and the recommended phase 2 dose of NBTXR3 was established at 42% of gross tumor volume.

Notably, one patient on Study 2019-1001 had a partial response 9 months after RT and has had durable local control for over two years. One other patient experienced local control that allowed unresectable disease to become resectable. Negative margin surgery ("R0 surgery") was achieved for this patient and pathological complete response was observed. The dose expansion part of the study will include more robust evaluation of patients with borderline resectable disease at study entry.

About Study 2019-1001
Pancreatic cancer (PC) is a rare, deadly disease. Given that surgery with R0 resection (i.e., macroscopically complete tumor removal with negative microscopic surgical margins) remains the only hope for long-term survival, clinical trials have investigated various neoadjuvant strategies—wherein patients receive anti-cancer drugs or radiation prior to surgery—to increase the surgery-eligible population while also increasing the R0 resection rate.

MD Anderson Study 2019-1001 is an open-label, single-arm, prospective phase I study consisting of two parts: (i) dose-escalation to determine the recommended phase 2 dose (RP2D); and (ii) expansion at RP2D.

The patient population will include adults (age ≥ 18 years) with borderline resectable (BR) or locally advanced (LA) PC that are radiographically non-metastatic at screening, and that have not previously received radiation therapy or surgery for pancreatic cancer. The complete dose escalation part recruited 11 patients with unresectable LAPC and the RP2D was established at 42% of gross tumor volume. Twelve additional patients with either LAPC or BRPC will be enrolled for the RP2D expansion.

The objectives of the study are the determination of dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), and the RP2D.

About NBTXR3
NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) as the primary development pathway. The company-sponsored phase I dose escalation and dose expansion study has produced favorable safety data and early signs of efficacy; and a phase III global registrational study was launched in 2021. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the phase III study.

Nanobiotix has also prioritized an Immuno-Oncology development program—beginning with a Company-sponsored phase I clinical study evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC, or lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a strategic collaboration strategy with world class partners to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies to evaluate NBTXR3 across tumor types and therapeutic combinations.

On November 14, 2022 Mustang Bio, Inc. ("Mustang") (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported financial results and recent corporate highlights for the third quarter ended September 30, 2022 (Press release, Mustang Bio, NOV 14, 2022, View Source [SID1234624005]).

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Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We continued to make progress advancing our portfolio of cell and gene therapies during the third quarter. Notably, we treated the first patient in our multicenter Phase 1/2 clinical trial to evaluate the safety and efficacy of MB-106, our first-in-class CD20-targeted, autologous CAR T cell therapy for the treatment of relapsed or refractory B-cell non-Hodgkin lymphomas ("B-NHL") and chronic lymphocytic leukemia ("CLL"). This first clinical trial under Mustang’s Investigational New Drug application ("IND") builds upon the initial, ongoing Phase 1/2 clinical trial taking place at Fred Hutchinson Cancer Center ("Fred Hutch"). In the Fred Hutch trial, MB-106 continues to demonstrate high efficacy and a favorable safety profile across patients with a wide range of hematologic malignancies. Results from the Waldenstrom macroglobulinemia ("WM") cohort of the Fred Hutch trial were recently presented at the 11th International Workshop for Waldenstrom’s Macroglobulinemia ("IWWM-11"), showing a 100% complete response ("CR") rate in patients with WM. Our MB-106 program was granted Orphan Drug Designation ("ODD") by the U.S. Food and Drug Administration ("FDA") for WM, and we plan to treat additional patients with WM in the Mustang-sponsored Phase 1 portion of our multicenter trial in order to support a fast-to-market Phase 2 strategy for this indication. We anticipate announcing early results from the Mustang-sponsored Phase 1 trial in December 2022."

"In summary, our CD20 CAR T remains our lead program, and we believe the product profile is favorable compared to the approved autologous CAR Ts, which are generating an annualized run rate of $3 billion in net sales, based on reported sales in the third quarter of 2022," said Dr. Litchman.

Recent Corporate Highlights:

In July 2022, Mustang announced that the first patient successfully received LV-RAG1 ex vivo lentiviral gene therapy to treat RAG1-SCID, in an ongoing Phase 1/2 multicenter clinical trial taking place in Europe. LV-RAG1 is exclusively licensed by Mustang for the development of MB-110, a first-in-class ex vivo lentiviral gene therapy for the treatment of RAG1-SCID.

In October 2022, Mustang announced that the first patient was treated in its multicenter, open-label, non-randomized Phase 1/2 clinical trial evaluating the safety and efficacy of MB-106, Mustang’s first-in-class CD20-targeted, autologous CAR T cell therapy for the treatment of relapsed or refractory B-NHL and CLL. This is the first MB-106 clinical trial under Mustang’s IND.

Also in October 2022, Mustang shared interim data from 28 patients treated in the initial, ongoing Phase 1/2 investigator-sponsored clinical trial at Fred Hutch. These data continue to support MB-106 as a viable CAR T cell therapy for B-NHLs and CLL. An ORR of 96% and CR rate of 75% were observed in a wide range of hematologic malignancies including follicular lymphoma ("FL"), CLL, diffuse large B-cell lymphoma, and WM. Twelve patients have experienced CR for more than 12 months (10 ongoing), including four patients with CR for more than two years and the longest patient with CR at 33 months. Six patients with initial partial response ("PR") at 28 days post-treatment improved to CR, presumably due to the demonstrated persistence of CAR-T cells in these patients, and all remain in ongoing CR. All three patients previously treated with CD19 Car-T cell therapy have responded to

treatment with MB-106. A favorable safety profile for MB-106 as an outpatient therapy remains, with no cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome ≥ Grade 3.

Additionally in October 2022, Mustang announced that results from the WM cohort and other interim data from the ongoing Phase 1/2 clinical trial of MB-106 at Fred Hutch were presented at IWWM-11 that took place in Madrid, Spain. Mustang’s MB-106 program was granted ODD by the FDA for WM, and Mustang plans to treat additional WM patients in the Mustang-sponsored Phase 1 portion of its multicenter trial in order to support a fast-to-market Phase 2 strategy for this indication.

Mustang expects to announce early results from the Mustang-sponsored multicenter MB-106 trial later this quarter.

Financial Results:

As of September 30, 2022, Mustang’s cash and cash equivalents and restricted cash totaled $92.4 million, compared to $108.4 million at June 30, 2022 and $110.6 million as of December 31, 2021, a decrease of $16.0 million for the quarter and a decrease of $18.2 million year-to-date.

Research and development expenses were $15.5 million for the third quarter of 2022, compared to $14.7 million for the third quarter of 2021. Non-cash, stock-based expenses included in research and development were $0.3 million for the third quarter of 2022, compared to $0.7 million for the third quarter of 2021.

General and administrative expenses were $3.4 million for the third quarter of 2022, compared to $2.4 million for the third quarter of 2021. Non-cash, stock-based expenses included in general and administrative expenses were $0.2 million for the third quarter of 2022, compared to $0.3 million for the third quarter of 2021.

Net loss attributable to common stockholders was $19.0 million, or $0.18 per share, for the third quarter of 2022, compared to a net loss attributable to common stockholders of $17.0 million, or $0.19 per share, for the third quarter of 2021.

On November 14, 2022 Midatech Pharma PLC (AIM: MTPH.L; Nasdaq: MTP), an R&D biotechnology company focused on improving the bio-delivery and biodistribution of medicines, reported the enrolment of the first patient into its Phase 1 study of MTX110 in recurrent glioblastoma (rGB) (NCT 05324501) at the Preston Robert Tisch Brain Tumor Center at Duke University, USA (Press release, Midatech Pharma, NOV 14, 2022, View Source [SID1234624004]).

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The Phase I study is an open-label, dose escalation study designed to assess the feasibility and safety of intermittent infusions of MTX110 administered by convection enhanced delivery (CED) via implanted refillable pump and catheter. The study aims to recruit two cohorts, each with a minimum of four patients; the first cohort will receive MTX110 only and the second cohort will receive MTX110 in combination with lomustine.

Midatech has previously reported encouraging results from a Phase I study of MTX110 in diffuse intrinsic pontine glioma ("DIPG") conducted by University of California, San Francisco with an additional Phase I study of MTX110 in DIPG conducted by Columbia University expected to report shortly. In addition, a Phase I study of MTX110 in medulloblastoma is being undertaken at the University of Texas.

MTX110 has been granted Orphan Drug and Fast Track designations by the FDA and Orphan Medicinal Product designation by EMA.

Commenting, Dmitry Zamoryakhin, MD, MBA, CSO of Midatech, said: "rGB is a devastating and incurable cancer marked by short survival rates and universal recurrence. A start of recruitment into the MAGIC-G1 study marks a significant step towards developing a potential new treatment paradigm for patients with this devastating disease that currently has limited effective treatment options".

Commenting, Annick Desjardins, MD, FRCPC, neuro-ongologist, professor of neurosurgery and neurology at Duke University and study’s principal investigator, said: "We are excited to be a leading center for the MAGIC-G1 study that is looking to overcome the limited penetration of panobinostat through the blood-brain barrier by its direct administration into the tumor, thus also potentially avoiding systemic toxicity."

About Glioblastoma (GB)

GB is the most common and devastating primary malignant brain tumour in adults encompassing 14.3% of all primary brain and central nervous system neoplasms(1). With an incidence of approximately 3.2 per 100,000 population in the USA, approximately 12,300 people in the USA will be diagnosed with GB per annum. Standard of care for treatment of GB is typically maximal surgical resection followed by radiotherapy plus concomitant and maintenance temozolomide chemotherapy with or without the Optune device . Notwithstanding, the multidisciplinary approach, almost all patients experience tumour progression with nearly universal mortality. The median survival from initial diagnosis is less than 21 months(2).

Currently, no standard of care is established for rGB.

About MTX110

MTX110 is a water-soluble form of panobinostat free base, achieved through complexation with hydroxypropyl-β-cyclodextrin (HPBCD), that enables convection-enhanced delivery (CED) at potentially chemotherapeutic doses directly to the site of the tumour. Panobinostat is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). The currently available oral formulation of panobinostat lactate (Farydak) is not suitable for treatment of brain cancers owing to poor blood-brain barrier penetration and inadequate brain drug concentrations. Based on favourable translational science data, MTX110 is being evaluated clinically as a treatment for DIPG (NCT03566199, NCT04264143) and recurrent medulloblastoma (NCT04315064), and preclinically for treatment of glioblastoma (SNO 2020 Abstract TMOD-27). MTX110 is delivered directly into and around the patient’s tumour via a catheter system (e.g. CED or fourth ventricle infusions) to bypass the blood-brain barrier. This technique exposes the tumour to very high drug concentrations while simultaneously minimising systemic drug levels and the potential for toxicity and other side effects. Panobinostat has demonstrated high potency against DIPG tumour cells in in vitro and in vivo models, and in a key study it was the most promising of 83 anticancer agents tested in 14 patient-derived DIPG cell lines (Grasso et al, 2015. Nature Medicine 21(6), 555-559).