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.

On April 4, 2023 Mythic Therapeutics, a biotechnology company focused on the development of next-generation antibody-drug conjugate-based therapies for the treatment of a wide range of cancers, reported that the first subject has been dosed in the Phase 1 KisMET-01 clinical trial of MYTX-011 (Press release, Mythic Therapeutics, APR 4, 2023, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-announces-first-subject-dosed-in-phase-1-kismet-01-clinical-trial-of-cmet-targeting-antibody-drug-conjugate-adc-mytx-011-for-the-treatment-of-non-small-cell-lung-cancer-nsclc [SID1234629805]). MYTX-011 is a cMET-targeting ADC being investigated for the treatment of patients with locally advanced, recurrent or metastatic non-small cell lung cancer (NSCLC).

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"Today’s announcement of our first subject dosed represents a significant step towards increasing the number of lung cancer patients eligible for treatment using ADCs, including those whose cancers express moderate cMET levels," said Brian Fiske, PhD, Chief Scientific Officer and Co-Founder at Mythic Therapeutics. "At Mythic, we are focused on our vision of unlocking the full potential of MYTX-011 as well as our broader pipeline of ADCs incorporating FateControl technology, which represents a fundamentally new paradigm for ADC therapies."

The KisMET-01 Phase I clinical trial is an open-label, multi-center, dose escalation and dose expansion study that will evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of MYTX-011 in subjects with locally advanced, recurrent or metastatic NSCLC. The study will be conducted in two parts. Part 1 will assess the safety and tolerability of MYTX-011 and identify the dose(s) to be studied in Part 2. Part 2 will include subjects with NSCLC with cMET overexpression or MET amplification/exon 14 skipping mutations, which are currently populations with an unmet medical need.

MYTX-011, a cMET-targeting ADC, leverages Mythic’s innovative FateControl technology, which allows ADCs to actively navigate inside of cells to potentially increase delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles.

The first patient was dosed at Sarah Cannon Research Institute (SCRI) at Tennessee Oncology in Nashville, Tennessee, under the care of Melissa Johnson, MD, Director, Lung Cancer Research, SCRI. "Although ADCs have been around for decades, their clinical benefit has been limited to a subset of diseases and targets with specific characteristics, such as high levels of target expression," said Dr. Johnson. "With cMET overexpression occurring in up to 70% of NSCLC tumors,[1],[2] patients need better treatment options to address lower levels of cMET target expression. We look forward to evaluating the potential of MYTX-011 to expand the use and eligibility of ADCs for patients with NSCLC."

More information about the clinical trial is available at clinicaltrials.gov (identifier: NCT05652868).

On April 3, 2023 Biodexa Pharmaceuticals PLC (AIM: BDRX.L; Nasdaq: BDRX), a drug delivery technology company focused on improving the bio-delivery and bio-distribution of medicines, reported that, in accordance with the terms of previously issued Pre-Funded Warrants and the associated Price Adjustment Mechanism under the Private Placement, it has issued an additional 10,508,394 Pre-Funded Warrants, calculated by dividing the aggregate subscription amount by 90% of the average of the daily volume weighted average prices of the five trading days prior to the date of this announcement (Press release, Midatech Pharma, APR 4, 2023, View Source [SID1234629804]). The issue of such Pre-Funded Warrants results in the total number of Pre-Funded Warrants issued under the Private Placement being 12,444,558, accounting for the Company’s completed Consolidation and Ratio Change, as detailed in its circular dated 7 March 2023

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Each Pre-Funded Warrant is immediately exercisable into one new ADS (equivalent to five new Ordinary Shares) with an exercise price of US$0.0004.