On April 4, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported the publication of a paper in Molecular Therapy titled ‘Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR (Press release, Autolus, APR 4, 2023, View Source [SID1234629810]).

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While CD19 CAR T cell therapy has had remarkable success in the treatment of B-cell malignancy, a proportion of patients may relapse with CD19 negative escape. Relapses due to antigen escape are a common cause of treatment failure in pediatric B-ALL. A solution to this is the co-targeting of a 2nd B-lineage antigen. CD22 is expressed early in B-cell development up until plasma cell differentiation and is expressed broadly by B-cell malignancies. Co-targeting of CD19 and CD22 is challenging for two reasons. Firstly, CD22 is a difficult CAR target being bulky and expressed at low density. Secondly, the optimal way of designing a CAR T cell which targets two antigens simultaneously has not been established.

In this paper, the Autolus research team first develop a highly sensitive CD22 CAR which can recognize target antigen even if CD22 is expressed at low density. Secondly, they explore a co-transduction approach with the clinically proven Autolus CD19 CAR, Obecabtagene autoleucel (obe-cel). The advantage of a co-transduction approach is that expression of neither obe-cel nor the new CD22 CAR are perturbed. This new CD19/CD22 CAR T cell therapeutic (AUTO1/22) was found to be effective in a mouse model of B-Cell Acute Lymphoblastic Leukemia (B-ALL) with CD19 negative escape.

AUTO1/22 is currently being tested in a pediatric study of relapsed/remitting (r/r) B-ALL [NCT02443831].

"CD22 targeting and CD19/CD22 co-targeting are challenging technical problems in the field," said Martin Pule, Chief Scientific Officer, and Founder of Autolus. "Development of AUTO1/22 in this paper represents the state-of-the-art with a high-sensitivity CD22 receptor and efficient co-targeting."

"I am delighted to see publication of the pre-clinical data for AUTO1/22," added Christian Itin, Chief Executive Officer of Autolus. "This work builds on our success with CD19 targeting with obe-cel and represents a significant evolution of our obe-cel platform. AUTO1/22 may reduce CD19 negative escape in children with B-ALL and may have broader applications in improving outcomes in other B-cell malignancies."

1.Evangelia Kokalaki, Biao Ma, Mathieu Ferrari et al. Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR. Molecular Therapy. The full publication can be viewed here.

On April 4, 2023 Step Pharma, the world leader in CTPS1 inhibition for the targeted treatment of cancer, reported the publication of compelling preclinical data detailing the therapeutic potential of inhibiting CTPS1 in haematological malignancies (Press release, Step Pharma, APR 4, 2023, View Source [SID1234629809]).

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The data, published in HemaSphere (the official journal of the European Hematology Association (EHA) (Free EHA Whitepaper)), describe the identification and characterisation of CTP synthase 1 (CTPS1), an enzyme that catalyses a rate-limiting step in pyrimidine synthesis, as a novel therapeutic target in T cell and B cell malignancies.

Step Pharma’s selective CTPS1 inhibitors induced cell death of neoplastic lymphoid cells in vitro and demonstrated anti-tumour activity in vivo in models of both T cell and B cell malignancies.

STP938, a first-in-class, highly selective, orally bioavailable inhibitor of CTPS1 recently entered a Phase 1/2 trial for T cell and B cell lymphomas (NCT05463263) and study sites are open in the UK and the USA.

Lymphoma is the most common haematological malignancy. Despite improvements in patient survival with modern immunochemotherapy treatments, there remains a significant need for novel targeted agents to treat both T cell and B cell malignancies.

On March 31, 2023, Selecta Biosciences, Inc. (the "Company") reported to have entered into a Fourth Amendment to Loan and Security Agreement (the "Fourth Amendment"),which amended that certain Loan and Security Agreement, dated August 31, 2020, between the Company, Oxford Finance LLC, as collateral agent and as a lender, and Silicon Valley Bank, a division of First-Citizens Bank & Trust Company (successor by purchase to the Federal Deposit Insurance Corporation as Receiver for Silicon Valley Bridge Bank, N.A. (as successor to Silicon Valley Bank)) ("Silicon Valley Bank") as a lender (as amended by that certain First Amendment to Loan and Security Agreement, dated September 7, 2021, that certain Second Amendment to Loan and Security Agreement, dated March 21, 2022, that certain Third Amendment to Loan and Security Agreement, dated September 20, 2022, and as further amended by the Fourth Amendment, the "Loan Agreement") (Filing, 8-K, Selecta Biosciences, APR 4, 2023, View Source [SID1234629808]).

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The Fourth Amendment, among other things, relieves the Company of the requirement to maintain all Collateral Accounts (as such term is defined in the Loan Agreement) with Silicon Valley Bank, and instead requires the Company to hold an amount equal to the lesser of (i) 100% of the Company’s consolidated cash and (ii) 150% of the then-outstanding Obligations (as such term is defined in the Loan Agreement) in Collateral Accounts with Silicon Valley Bank that are subject to a Control Agreement (as such term is defined in the Loan Agreement) in favor of Silicon Valley Bank.

The foregoing description of the Fourth Amendment is a summary thereof, and is qualified in its entirety by reference to the full text of the Fourth Amendment, which is filed herewith as Exhibit 10.1, and is incorporated herein by reference.

On April 4, 2023 NuCana plc (NASDAQ: NCNA) reported financial results for the fourth quarter and year ended December 31, 2022 and provided an update on its broad clinical program with its transformative ProTide therapeutics (Press release, Nucana BioPharmaceuticals, APR 4, 2023, View Source [SID1234629807]).

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As of December 31, 2022, NuCana had cash and cash equivalents of £41.9 million compared to £50.8 million as of September 30, 2022 and £60.3 million at December 31, 2021. NuCana continues to advance its various clinical programs and reported a net loss of £15.2 million for the quarter ended December 31, 2022, as compared to a net loss of £13.6 million for the quarter ended December 31, 2021. Net loss for the year ended December 31, 2022 was £32.0 million, compared to a net loss of £40.5 million for the year ended December 31, 2021. Basic and diluted loss per share was £0.29 for the quarter and £0.61 for the year ended December 31, 2022, as compared to £0.26 per share for the comparable quarter and £0.78 for the year ended December 31, 2021.

"We had a very productive 2022 as we achieved numerous development milestones for NUC-3373 and NUC-7738," said Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer. "During the year, we determined the recommended Phase 2 dose for both NUC-3373 and NUC-7738. Both of these product candidates have progressed to Phase 2 development and are being evaluated in novel combinations and additional indications. We also presented promising efficacy and safety data that continue to demonstrate the potential of our ProTides to offer more effective and safer treatment options for patients with cancer."

Mr. Griffith continued: "Looking ahead to 2023, we expect to make several important data announcements across our pipeline. For NUC-3373, which we believe has the potential to replace 5-FU across multiple tumor types, we plan to provide updates from three clinical studies: the Phase 2 part of NuTide:302 in which NUC-3373 is being combined with leucovorin and either irinotecan (NUFIRI) or oxaliplatin (NUFOX) plus bevacizumab in patients with second-line colorectal cancer; NuTide:323, a randomized Phase 2 study of NUFIRI plus bevacizumab compared to the standard of care FOLFIRI plus bevacizumab for the second-line treatment of patients with colorectal cancer; and NuTide:303, a Phase 1b/2 modular study of NUC-3373 in combination with pembrolizumab in patients with various solid tumors and in combination with docetaxel in patients with lung cancer."

Mr. Griffith added: "NuTide:323 will include 171 patients and compare NUFIRI plus bevacizumab based on weekly and alternate weekly NUC-3373 dosing schedules to FOLFIRI plus bevacizumab. We believe NuTide:323 has the potential to provide meaningful data in our target population of second-line patients with colorectal cancer and enable us to optimize a Phase 3 study. Additionally, given 5-FU’s broad usage across multiple tumor types, we are excited to be expediting the NuTide:303 study, which is designed to identify novel combinations and additional indications for development."

Mr. Griffith said: "For NUC-7738, which is based on a novel nucleoside, 3’-deoxyadenosine, we look forward to announcing data from the Phase 2 part of the NuTide:701 study which is investigating NUC-7738 both as a monotherapy in patients with solid tumors and in combination with pembrolizumab in patients with melanoma."

Mr. Griffith concluded: "Overall, we are pleased with the progress we have made with NUC-3373 and NUC-7738 in 2022. With a cash runway expected to fund operations into 2025, we look forward to an exciting year for NuCana."

2023 Anticipated Milestones

NUC-3373 (a ProTide transformation of 5-FU)

In 2023, NuCana expects to:

Announce data from the Phase 2 (NuTide:302) study of NUC-3373 combined with irinotecan and bevacizumab and in combination with oxaliplatin and bevacizumab in second-line patients with colorectal cancer;

Announce data from the randomized, controlled Phase 2 (NuTide:323) study of NUC-3373 in combination with irinotecan/bevacizumab for the second-line treatment of patients with colorectal cancer; and

Announce data from the Phase 1b (NuTide:303) modular study of NUC-3373 in combination with pembrolizumab in patients with various solid tumors and in combination with docetaxel in patients with lung cancer to identify additional indications for development.

NUC-7738 (a ProTide transformation of 3’-deoxyadenosine)

In 2023, NuCana expects to:

Announce data from the Phase 1 part of the NuTide:701 study of NUC-7738 in patients with solid tumors; and

Announce data from the Phase 2 part of the NuTide:701 study of NUC-7738 both as monotherapy in patients with solid tumors and in combination with pembrolizumab in patients with melanoma.

On April 4, 2023 Nerviano Medical Sciences Srl (Company), a member of NMS Group and a clinical stage company discovering and developing innovative therapies for the treatment of cancer, reported that data from the Phase I/II clinical study of NMS-03592088 in Acute Myeloid Leukemia will be reported in an oral presentation by Dr. Antonio Curti, MD, PhD, IRCCS Azienda Ospedaliero-Universitaria di Bologna, at the upcoming AACR (Free AACR Whitepaper) Annual Meeting which will be held April 14 – 19, Orange County Convention Center, Orlando, Florida (Press release, Nerviano Medical Sciences, APR 4, 2023, View Source [SID1234629806]).

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Details of the upcoming oral presentation are as follows:

Title: NMS-03592088, a novel, potent FLT3, KIT and CSF1R inhibitor with activity in FLT3 positive acute myeloid leukemia patients with prior FLT3 inhibitor experience
Presenter: Dr. Antonio Curti, Istituto di Ematologia Seràgnoli, IRCCS Azienda Ospedaliero-Universitaria di Bologna
Session: CTMS01 – Novel Clinical Trials for Hematological Malignancies- CT025
Session Date/Time: April 16, 2023, 4:05 PM – 4:15 PM
Location: Valencia A – Convention Center

The data are embargoed until the day of the presentation. A copy of the oral presentation will be available at www.nervianoms.com following presentation at the meeting.
– – – – – – – – – – – –

About NMS-03592088

Acute Myeloid Leukemia (AML) is a rapidly progressing hematologic malignancy that most frequently develops in older adults. FLT3 mutations occur in approximately 30% of AML patients and are associated with aggressive disease, higher relapse rates and worse survival. Despite the approval of FLT3 inhibitors midostaurin and gilteritinib that improve the treatment of FLT3 positive patients, the prognosis of patients with relapsed or refractory disease is poor.

NMS-03592088 is a novel, potent inhibitor of FLT3, KIT and CSF1R, all relevant targets in AML. NMS-03592088 showed superior preclinical activity compared with approved FLT3 inhibitors in different FLT3-driven models. In addition, NMS-03592088 is active on FLT3 gatekeeper mutation F691L causing resistance to first generation FLT3 inhibitors.

MKIA-088-001 is a Phase I/II study of NMS-03592088 administered as single agent in relapsed or refractory AML and CMML patients. The trial is currently open for enrollment.