On March 25, 2024 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumors, reported recent corporate developments and financial results for the year ended December 31, 2023 (Press release, Marker Therapeutics, MAR 25, 2024, View Source [SID1234641449]).

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"The progress achieved in 2023 we believe establishes a robust foundation for Marker and sets the stage for continued advancement in our clinical programs and business operations in the upcoming year," commented Juan Vera, M.D. President and Chief Executive Officer of Marker Therapeutics. "A pinnacle of last year’s success was the Phase 1 lymphoma study milestone, where we observed a sustained complete response in our first study participant treated with MT-601 following CAR T relapse. This patient relapsed within 90 days of CAR T therapy but has remained in a complete remission for at least six months after MT-601 treatment, indicating that MT-601 has superior durability in this study participant. The promising clinical and non-clinical observations from our lymphoma study reinforced our strategic decision, made public this January, to prioritize the development of MT-601 in patients with lymphoma who have failed or are ineligible for CAR T therapy. Focusing on this unique niche of patients and by targeting multiple antigens, our approach differs significantly from competitors, and we believe that MT-601 could address an unmet medical need in this patient population with a better safety profile and at lower costs when compared to gene-modified cell therapy approaches."

Further bolstering Marker’s position is the award of $2 million in non-dilutive funding from the NIH last year, which is instrumental in supporting the advancement of the Company’s MT-401 "Off-the-Shelf" (MT-401-OTS) program in patients with Acute Myeloid Leukemia (AML).

Dr. Vera added, "This award is expected to enable us to proceed with the OTS program without affecting our ongoing study for patients with lymphoma. Decreasing time to treatment is critical for rapidly progressing cancers, such as patients with minimal residual disease (MRD) in AML."

Utilizing an OTS product manufactured from healthy donors will help to bypass the treatment delay that is associated with patient-specific manufacture and should shorten the time until the product is made available to patients, while reducing manufacturing costs. Additionally, receiving Orphan Drug Designation (ODD) by the European Medicines Agency (EMA) substantiates the potential impact of MT-401 in patients with AML and presents an opportunity to develop the therapy on an expedited basis.

Marker also executed a comprehensive non-dilutive agreement with Cell Ready which included a sale of select cell manufacturing assets from Marker for approximately $19 million in cash. This major transaction, which we expect will enable a reduction of overhead expenses of about $11 million annually, not only improves our financial health but, we believe, also positions us uniquely in the cell therapy industry — a sector where such significant non-dilutive funding and operational savings are remarkably rare. This strategic foresight, together with the drawdowns available from our grant funds, should extend the cash runway into the fourth quarter of 2025.

"These accomplishments underline our commitment to driving scientific innovation, our vision in making major impact with our novel multiTAA technology for patients in need, and our emphasis on cash preservation and operational excellence. As we have pivoted into 2024, we remain poised to advance our clinical endeavors with the goal of introducing transformative therapies to the market and improving patient outcomes," concluded Dr. Vera.

2023 PROGRAM UPDATES & OPERATIONAL HIGHLIGHTS

MT-601 (Lymphoma)

Non-Clinical Data on MT-601

- Marker developed a long-term in vitro killing assay 1) to investigate resistance mechanisms after CAR T cell treatment, and 2) to analyze if MT-601 (targeting 6 TAAs) can eliminate CAR-resistant lymphoma cells.

- Anti-CD19 CAR T cell treatment killed 98% of lymphoma cells in vitro. However, after three weeks, CD19-negative tumor cells started to grow. Further anti-CD19 CAR T cell treatments were ineffective as these tumor cells lack target antigen (CD19) expression (Pre-Clinical Data in Lymphoma, May 31, 2023).

- Treatment with MT-601 demonstrated long-term growth inhibition (over three weeks) of CAR-resistant lymphoma cells, highlighting that MT-601 has the potential to effectively treat CD19 CAR-resistant tumors (Press Release, May 31, 2023).

Clinical Highlights

- Phase 1 multicenter APOLLO trial (clinicaltrials.gov identifier: NCT05798897), investigating MT-601 in patients with lymphoma who relapsed or are ineligible for anti-CD19 CAR T cell therapies, was selected as lead program based on promising preliminary clinical results and non-clinical proof-of-concept data.

- The first study participant, a 57-year-old female with diffuse large B cell lymphoma (DLBCL), was enrolled in the Phase 1 dose escalation stage of the trial after failing 4 prior lines of therapy, including relapsing within 90 days of anti-CD19 CAR T cell therapy. Without prior lymphodepletion, the participant was treated with MT-601. In December 2023, the Company announced that the study participant tolerated initial dose level well and had maintained a complete response to therapy six months after initial treatment with MT-601 (Press Release, December 11, 2023).

The Company is enrolling additional patients in the Phase 1 APOLLO trial and expects to report further data in the first half of 2024.

- MT-601 designated non-proprietary name "Neldaleucel" by United States Adopted Name (USAN) Counsel and International Nonproprietary Names (INN) Expert Committee.

MT-601 (Pancreatic)

- Investigational New Drug (IND) application cleared by U.S. Food and Drug Administration (FDA) for multicenter Phase 1 trial of MT-601 in patients with metastatic pancreatic cancer in combination with front-line chemotherapy.

- Clinical advancement will be pending additional financial support from non-dilutive grant activities.

MT-401-OTS (Acute Myeloid Leukemia or Myelodysplastic Syndrome)

- U.S. FDA has granted an Investigational New Drug (IND) to investigate MT-401 as an "Off-the-Shelf" (MT-401-OTS) product in patients with AML or Myelodysplastic Syndrome (MDS). MT-401-OTS is manufactured from healthy donors and a cellular inventory has been established with ongoing efforts to expand.

- Marker announced non-clinical proof-of-concept data supporting the clinical benefits of MT-401-OTS in AML.

- The Company has secured $2M in non-dilutive funding from the NIH Small Business Innovation Research (SBIR) program. These funds will support the clinical investigation of MT-401-OTS in patients with AML without affecting the ongoing Phase 1 APOLLO study in patients with lymphoma.

- Granted ODD from the Committee for Orphan Medicinal Products of the EMA for the treatment of patients with AML in 2023. ODD was received from the U.S. FDA in 2020.

- Clinical program initiation of MT-401-OTS anticipated for the second half of 2024.

2023 CORPORATE HIGHLIGHTS

- Announced clinical pipeline prioritization in January 2024 to strategically focus on MT-601 in patients with lymphoma. This announcement also included program updates that highlighted the potential of the Company’s MT-401-OTS program for AML.

- Appointed Juan Vera, M.D., as President and Chief Executive Officer and Monic Stuart, M.D., MPH, as Chief Medical Officer. Dr. Vera was also appointed the Company’s Principal Financial and Accounting Officer.

- On June 26, 2023, Marker completed a non-dilutive transaction with Cell Ready, under which Cell Ready purchased certain cell manufacturing assets from Marker for approximately $19 million in cash. On February 22, 2024, Marker entered into a Master Services Agreement for Product Supply with Cell Ready. Under this agreement, Cell Ready will perform a wide variety of services for Marker, including research and development, and manufacturing in support of Marker’s clinical trials.

- Terminated common stock purchase agreement with Lincoln Park Capital.

- Extended financial runway into the fourth quarter of 2025.

FISCAL YEAR 2023 FINANCIAL HIGHLIGHTS

Cash Position and Guidance: At December 31, 2023, Marker had cash and cash equivalents of $15.1 million. The Company believes that its existing cash and cash equivalents will fund its operating expenses into the fourth quarter of 2025, inclusive of available drawdowns from grant funds.

R&D Expenses: Research and development expenses were $10.4 million for the year ended December 31, 2023, compared to $12.0 million for the year ended December 31, 2022.

G&A Expenses: General and administrative expenses were $7.5 million for the year ended December 31, 2023, compared to $11.3 million for the year ended December 31, 2022.

Net Loss: Marker reported a net loss of $8.2 million for the year ended December 31, 2023, compared to a net loss of $29.9 million for the year ended December 31, 2022.

About multiTAA-specific T cells

The multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood capable of recognizing a broad range of tumor antigens. Since multiTAA-specific T cells are not genetically engineered, Marker believes that its product candidates will be easier and less expensive to manufacture, with reduced toxicities, compared to current engineered CAR-T and TCR-based approaches, and may provide patients with meaningful clinical benefits. As a result, Marker believes that its portfolio of T cell therapies has a compelling product profile, as compared to current gene-modified CAR-T and TCR-based therapies.

On March 25, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported a preliminary update on recent clinical activity and expected near term milestones for its lead program MB-106 for the treatment of Acute Myeloid Leukemia (AML) following its Fiscal Year 2023 filing with the Securities and Exchange Commission (Press release, Moleculin, MAR 25, 2024, View Source [SID1234641409]). As previously announced, the Company will host a conference call and live audio webcast, today, March 25, 2024, at 8:30 AM ET (details below).

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"We remain highly encouraged by the positive data seen to-date in our Phase 1B/2 AnnAraC trial for AML," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. "With a CRc rate of 60% as 2nd line therapy and with 50% of those being full CRs, AnnAraC has the potential to offer 2nd line patients a viable alternative, regardless of prior treatments or mutations. Importantly, we recently visited prominent key opinion leaders in Europe and the U.S. Without exception, they each believe there remains a significant unmet need for 2nd line AML therapies, that our results in 2nd line subjects are significant, and that, if approved, they would use Annamycin in their practice. We are seeing genuine enthusiasm for how Annamycin might change the paradigm."

"Understanding the continuing unmet need in AML is key to understanding Moleculin’s opportunity. It is so key that we created an informative animation of the patient journey to help investors realize our potential in AML. In brief, even though tremendous effort has been focused on targeted therapies in AML and five new drugs have been approved for 2nd line use, they are only expected to result in a positive outcome for about 7% of the total AML population. We believe that leaves nearly 60% of AML patients without a viable path to lasting remission. At the rate indicated by our latest data, Annamycin could more than double the number of 2nd line patients achieving a complete response from all the currently approved targeted therapies combined," added Mr. Klemp.

"Our growing body of data are now propelling our clinical and regulatory strategies toward our next phase of development. We are preparing for an End of Phase 2 meeting with FDA and believe following this meeting we will be in a position to commence a pivotal registration study as a 2nd line therapy in AML before year end," concluded Mr. Klemp.

Ongoing AML Clinical Trial Overview

The Company is currently conducting its Phase 1B/2 clinical trial evaluating Annamycin in combination with Cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as AnnAraC) for the treatment of subjects with AML as both first line therapy and for subjects who are refractory to or relapsed after induction therapy (MB-106). clinicaltrialsregister.eu: EudraCT 2020-005493-10 or clinicaltrials.gov: NCT05319587.

During 2023, Moleculin commenced its MB-106 clinical trial with AnnAraC for the treatment of AML in an all-comers trial, accepting subjects without regard to the number of prior therapies in the Phase 1 portion with a limit of two prior therapies in the Phase 2 portion. Nine clinical sites in Poland and Italy have been activated for the MB-106.

To date, 20 subjects have been enrolled in the full MB106 Phase 1B/2 study with two subjects not yet evaluable. At the end of January 2024, the Company completed recruiting the desired number of 2nd line subjects and began preparation for an End of Phase 2 (EoP2) meeting with the FDA. In addition, Moleculin expanded the MB-106 study protocol to include 1st line subjects to provide data to enable the designing of a potential confirmatory Phase 3 post-approval study, however, do not expect the addition of this cohort to delay the EoP2 meeting. The study has recruited three 1st line subjects to date with one CR and one not yet evaluable.

Moleculin’s current planned pathway for approval for Annamycin in combination with Cytarabine for the treatment of AML is as a 2nd line therapy. Therefore, the focus is primarily on securing an accelerated approval pathway for the treatment of 2nd line subjects (those who were relapsed from or refractory to a 1st line AML therapy, regardless as to whether the subject was deemed "fit" or "unfit"). Moleculin has begun recruiting 1st line subjects into this trial to provide data for a possible future confirmatory Phase 3 clinical trial in 1st line patients.

Summary of MB-106 Data

A summary table of the MB-106 preliminary results, which are subject to change, is shown below. The total CRs in both Phases to date in MB-106 represent a complete response composite (CRc) rate of 39% in all currently evaluable, intent to treat subjects (n= 18) with two additional subjects recruited not yet evaluable. These subjects had 0-6 prior therapies. This is comprised of a CR rate of 33% and CRi of 6%. Durability data are developing with one CRc having relapsed to date. The first CR subject was treated in February 2023 and remains durable after over a year and continues in remission. Durability of CRs is confirmed by repeat bone marrow aspirates (BMAs).The median age of all subjects recruited is 69, ranging from 19 to 78. Median durability will be established as the trial data mature. This trial may enroll up to 28 subjects, however, having already recruited the desired number of 2nd line subjects to support an EoP2 meeting with the FDA, the Company may elect to complete this trial with fewer than 28 subjects.

The trial continues recruitment for treatment as 1st line and 3rd line therapy. Since Moleculin intends to position AnnAraC for approval as a 2nd line therapy, the Company believes that the most important data from this trial are the results in 2nd line subjects (excluding subjects who are either 1st line or 3rd line and beyond). When stratified for that population (n=10), the CRc rate is 60%, being comprised of a CR rate of 50% and a CRi of 10%.

Table 1 – Summary of Annamycin Responses in MB-106 as of March 19, 2024

Study

Study MB-106 Combination Therapy– Phase 1B/2 All Lines (Range 1-7)

Study MB-106Combination Therapy– Phase 1B/2 As 1st Line

Study MB-106Combination Therapy– Phase 1B/2 As 2nd Line Only

All Subjects

Recruited

20

3

10

Subjects Not Yet Evaluable

2

1

0

Subjects Evaluable To Date

18

2

10

Subjects Evaluable Not Dosed Per Protocol

2

0

1

Median Prior Therapies

1

0

1

Median Age – Years (Range)

69 (19-78)

49 (19-69)

71 (53 – 78)

Complete Responses (CR)

6

1

5

CR with incomplete recovery (CRi)

1

0

1

Total Complete Response(s) (CRc)

7

1

6

Complete Response (CR) Rate

33%

50%

50%

Complete Response Composite (CRc) Rate

39%

50%

60%

Partial Responses (PRs)

2

0

1

CRc Relapsed To Date

1

0

1

BMT To Date

1

0

1

Durability of CR

Developing

Developing

Developing

(1,2,3,4)

(2,3,4)

(2,3,4)

Notes for Table 1: 1) The 19th subject, being treated as a 3rd line therapy, had two BMAs tested where they have been inconclusive, and we are awaiting further testing. This subject will move the CRc in the "MB-106 Phase 1B/2 All Lines" column to either 42% or 37% (n=19). The 20th subject is a first-line therapy subject and has just begun treatment; 2) Data from MB-106 is for intent to Treat subjects; 3) Data from MB-106 is preliminary and subject to change; and 4) Durability is developing.

Expected 2024 MB-106 Milestones

●

Complete MB-106 Phase 1B/2 clinical trial.

●

Present topline data from MB-106 clinical trial.

●

Report outcome of MB-106 End of Phase 2 Meeting.

●

Initiate pivotal program.

Conference Call and Webcast

Moleculin management will host its quarterly conference call and webcast for investors, analysts, and other interested parties Monday, March 25, 2024, at 8:30 AM ET.

Interested participants and investors may access the conference call by dialing (877) 407-0832 (domestic) or (201) 689-8433 (international) and referencing the Moleculin Biotech Conference Call. The live webcast will be accessible on the Events page of the Investors section of the Moleculin website, moleculin.com, and will be archived for 90 days.

On March 25, 2024 Nkarta presented its corporate presentation (Press release, Nkarta, MAR 25, 2024, View Source [SID1234641410]).

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On March 25, 2024 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported the pricing of an underwritten offering of 21,010,000 shares of its common stock at a price of $10.00 per share and pre-funded warrants to purchase 3,000,031 shares of common stock (Press release, Nkarta, MAR 25, 2024, View Source [SID1234641411]). The pre-funded warrants are being sold at a price of $9.9999 per warrant, which represents the per share offering price for the common stock less the $0.0001 per share exercise price.

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New and existing investors participated in the offering, including Adage Capital Partners LP, Boxer Capital, Commodore Capital, Cormorant Asset Management, an affiliate of Deerfield Management, EcoR1 Capital, Janus Henderson Investors, OrbiMed, RA Capital Management, Ridgeback Capital Investments, Samsara BioCapital, SR One, and a leading mutual fund.

Gross proceeds to Nkarta from this offering are approximately $240.1 million, before deducting underwriting discounts and commissions and offering expenses. Nkarta intends to use the net proceeds from the offering to fund the continued research and clinical development of NKX019, the continued buildout of internal manufacturing capabilities, and for working capital and for general corporate purposes. The offering is expected to close on or about March 27, 2024, subject to customary closing conditions.

Leerink Partners, TD Cowen, Stifel and Mizuho are acting as joint bookrunners for the offering.

All securities in the offering are to be issued and sold by Nkarta. The offering was conducted pursuant to a shelf registration statement (File No. 333-270680), which was initially filed with the Securities and Exchange Commission ("SEC") on March 17, 2023 and declared effective by the SEC on May 5, 2023. The offering was made only by means of a prospectus supplement and accompanying prospectus describing the terms of the offering. Copies of the prospectus supplement and the accompanying prospectus relating to this offering may be obtained by contacting the following: Leerink Partners LLC, Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, or by telephone at (800) 808-7525 ext. 6105, or by email at [email protected]; Cowen and Company, LLC, 599 Lexington Avenue, New York, NY 10022, by telephone at (833) 297-2926, or by email at [email protected]; Stifel, Nicolaus & Company, Incorporated, Attention: Prospectus Department, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by telephone at (415) 364-2720 or by email at [email protected]; Mizuho Securities USA LLC, Attention: Equity Capital Markets, 1271 Avenue of the Americas, 3rd Floor, New York, New York 10020, by telephone at (212) 205-7602 or by email at [email protected]. These documents may also be obtained for free on the SEC’s website located at View Source

This press release does not constitute an offer to sell or the solicitation of an offer to buy the securities described herein, nor shall there be any offer, solicitation or sale of these securities in any state or 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 jurisdiction.

On March 25, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the U.S. Food and Drug Administration (FDA) has issued Complete Response Letters (CRLs) for the Biologics License Application (BLA) for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL), each after two or more lines of systemic therapy (Press release, Regeneron, MAR 25, 2024, View Source [SID1234641412]). The only approvability issue is related to the enrollment status of the confirmatory trials. The CRLs – one for R/R FL and one for R/R DLBCL – did not identify any approvability issues with the odronextamab clinical efficacy or safety, trial design, labeling or manufacturing.

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Regeneron has been actively enrolling patients in multiple Phase 3 trials for odronextamab as part of the OLYMPIA program – one of the largest clinical programs in lymphoma. As the OLYMPIA program is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes – including in earlier lines of therapy – in agreeing to the program, the FDA required that the trials include both dose-finding and confirmatory portions. Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion be agreed prior to resubmission. Regeneron is committed to working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. Regeneron plans on sharing updates on enrollment and regulatory timelines later this year.

Regulatory review of odronextamab remains ongoing by the European Medicines Agency (EMA) for the treatment of R/R DLBCL and R/R FL. In the European Union, odronextamab was granted Orphan Drug Designation in DLBCL and FL.

The potential use of odronextamab in R/R DLBCL and R/R FL is currently under clinical development and has not been approved by any regulatory authority.