On November 13, 2023 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 an update on operational progress and announced financial results for the third quarter of 2023 (Press release, Nanobiotix, NOV 13, 2023, View Source [SID1234637555]).

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"Our robust NBTXR3 clinical program continues to demonstrate potentially transformative efficacy and well-tolerated safety across indications and patient types, including elderly and vulnerable populations. We are pleased with the encouraging, expanded potential in locally advanced pancreatic cancer supported by initial Phase 1 data from our strategic collaboration with The University of Texas MD Anderson Cancer Center (MD Anderson) presented at this year’s AACR (Free AACR Whitepaper) and ESMO (Free ESMO Whitepaper) annual meetings," said Laurent Levy, co-founder of Nanobiotix and chairman of the executive board. "Additionally, strong Phase 1 data from Study 102 in locally advanced head and neck cancer demonstrated high and durable activity including a 64% complete response rate, a 16.9 months mPFS and 23.1 months mOS in evaluable patients, which is nearly double the survival reported in historical data. Further, we believe the Study 102 results inform next steps and further strengthen the hypotheses underlying the design of the ongoing global, registrational NANORAY-312 Phase 3 study for NBTXR3."

Laurent Levy continued, "Building on the momentum following our recent global licensing agreement with Janssen, we have raised €50.9 million in capital that includes a public offering and the partial execution of the second equity tranche from Johnson & Johnson Innovation, Inc. With the EIB cash covenant removed, our financial overhang addressed, and our cash runway extended, we are poised to successfully execute through several important catalysts and into the expected timeframe of the NANORAY-312 interim efficacy readout."

Third Quarter 2023 Operational Highlights, Subsequent Events, and Pipeline Status and Upcoming Milestones

Nanobiotix announced on July 10, 2023, that it had entered into a global exclusive licensing, co-development, and commercialization agreement with Janssen Pharmaceutica NV, a Johnson & Johnson company, for the investigational, potential first-in-class radioenhancer NBTXR3. The Company has received:
$30 million upfront cash licensing fee (received after June 30th, 2023)
$5 million first equity tranche received post signing
$20.2 million of $25 million second equity tranche received in recent capital raise

The Company remains eligible to receive:
Remaining €4.8 million from second equity tranche, subject to certain conditions
Up to $30M in-kind regulatory and development support for study NANORAY-312 provided at Janssen’s sole discretion
Success-based payments of up to $1.8B and tiered double-digit royalties on net sales of NBTXR3
Additional success-based potential development and regulatory milestone payments of up to $650 million, in the aggregate, for five new indications that may be developed by Janssen at its sole discretion
And up to $220 million, in the aggregate, per indication that may be developed by Nanobiotix in alignment with Janssen
The Company has raised gross proceeds of €50.9 million from a recent financing and second equity tranche from Johnson & Johnson Innovation, Inc. (JJDC) extends cash runway into 2Q 2025 assuming a development milestone. Gross proceeds are expected to increase to €55.5 million following subscription by JJDC to the remaining placement amount of the second tranche of €4.6 million.
Locally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC): Local Control as Single Agent Activated by Radiotherapy

NANORAY-312, a pivotal, global and randomized Phase 3 trial evaluating RT-activated NBTXR3 ± cetuximab vs RT ± cetuximab in elderly patients ineligible for cisplatin chemotherapy
Futility analysis following 25% of planned PFS events expected in H2 2024
Initial Phase 3 interim efficacy and safety data expected after 67% of planned PFS events in mid-2025
Study 102, a Phase 1 dose escalation and expansion trial evaluating RT-activated NBTXR3 in patients ineligible for cisplatin chemotherapy or intolerant to cetuximab
Topline safety and efficacy data presented as an oral presentation at the 65th Annual Meeting of the American Society for Radiation Oncology (ASTRO) supporting robust anti-tumor efficacy and well-tolerated profile in elderly patients with a high burden of comorbidity (n=56)
64% CR, 82% ORR in injected-lesion in the evaluable population (n=44) and median duration of response in the NBTXR3-injected lesion not yet reached
16.9 months mPFS and 23.1 months mOS in the evaluable population
Exploratory analyses presented at the 2023 Annual Congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) investigating additional signs of efficacy provide further support for hypotheses underlying the ongoing registrational Phase 3 NANORAY-312 study design
42.8 months mOS observed in the 81.8% of evaluable patients who had complete or partial response in the NBTXR3-injected lesion (36/44) compared to 18.1 months in All Patients Treated (n=56)
Positive correlation associated with objective response, PFS and OS extension with RT-activated NBTXR3 in the injected lesion
Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: Priming Immune Response Followed by an Anti-PD-1 Treatment

Study 1100, a Phase 1 dose escalation and expansion trial evaluating RT-activated NBTXR3 followed by an anti-PD-1 in patients with advanced cancers
Phase 1 dose expansion data update anticipated 1H 2024
Ongoing consultation with newly appointed CMO and our new partner on continuing discussions with the FDA for a potential registrational pathway for NBTXR3 in combination with an immunotherapy

Pancreatic, Lung and Others: Expanding NBTXR3 Opportunity Through a Strategic Collaboration with The University of Texas MD Anderson Cancer Center to Validate Tumor-Agnostic, Combination-Agnostic Therapeutic Profiles

Five ongoing clinical trials in advanced solid tumors:
Advanced Solid Tumors with Lung or Liver Metastases: Phase 1/2 study of RT-activated NBTXR3 plus an anti-PD-1/L-1 immune checkpoint inhibitor (NCT05039632)
First patient injected in July 2023
Recurrent or Metastatic Head and Neck Cancer: Phase 2 study of RT-activated NBTXR3 in combination with anti-PD-1 (NCT04862455)
Inoperable Non-Small Cell Lung Cancer (NSCLC): Phase 1 study of RT-activated NBTXR3 (NCT04505267)
Pancreatic Cancer: Phase 1 study of RT-activated NBTXR3 after cytotoxic chemotherapy for patients with locally advanced pancreatic cancer (LAPC), (NCT04484909)
Preliminary Phase 1b dose escalation safety data (July 30, 2023 cutoff) presented at American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2023 Special Conference on Pancreatic Cancer support feasibility and promising, durable anti-tumor efficacy of RT-activated NBTXR3
Tolerable safety with local endoscopic injection in 15 patients
92% (12/13) injected tumor disease control rate in evaluable patients
21 months mOS from diagnosis in evaluable patients
Additional preliminary signals of promising anti-tumor efficacy from the ongoing Phase 1 study (September 30, 2023 cutoff) presented at ESMO (Free ESMO Whitepaper) 2023 potentially help inform clinical trial development
Favorable safety profile and recommended dose established
23 months mOS observed in 15 patients
Esophageal Cancer: Phase 1 study of RT-activated NBTXR3 in combination with chemotherapy (NCT04615013)
Multiple clinical milestones in 2024:
Determination of RP2D in NSCLC trial
Completion of enrollment in Phase 1b dose expansion trial in pancreatic cancer
Initial Phase 1b/2 data in esophageal cancer
Third Quarter Financial Updates

Cash and Cash Equivalents

Nanobiotix reported cash and cash equivalents of €38.7 million (unaudited) as of September 30, 2023.

Based on the current operating plan and financial projections, we anticipate that the cash and cash equivalents of €38.7 million as of September 30, 2023, in conjunction with €50.9 million from the recent financing and partial execution of the second equity tranche from JJDC as well as a development milestone, extends the cash runway into the second quarter of 2025.

The gross proceeds of the Global Offering were €31.8 million including the Underwriter’s Option. Adding to this the €19.1 million gross proceeds from the restricted ADSs to be purchased by JJDC in the Concurrent Private Placement, the Company will receive aggregate gross proceeds of approximately €50.9 million (equivalent to approximately $53.8 million, based on an exchange rate of €1.00 = $1.0568, as published by Bloomberg on November 1, 2023), before deduction of underwriting commissions from the Global Offering and estimated offering expenses payable by the Company. Following the approval of the French Ministry of Economy and the subscription by JJDC for the Remaining Placement Amount, the aggregate gross proceeds would increase to approximately €55.5 million (equivalent to approximately $58.7 million) and would extend the cash runway to the end of the second quarter of 2025 (assuming the development milestone as above and excluding cash inflows from future non-dilutive or dilutive financing opportunities).

Successful Removal of the EIB Cash Covenant

As previously disclosed, the European Investment Bank (the "EIB") has agreed to the removal of the minimum cash and cash equivalent covenant from the Company’s EIB loan, effective October 13, 2023. As result of the financing with gross proceeds of €50.9 million, the company will prepay the EIB approximately €0.5 million (1% of €50.9M) of the €20.0 million milestone payment required under the EIB loan.

Conference Call and Webcast

Nanobiotix will host a conference call and live audio webcast on Tuesday, November 14, 2023, at 8:00 am ET / 2:00 pm CET, prior to the open of the U.S. market. During the call, Laurent Levy, chief executive officer, and Bart van Rhijn, chief financial officer, will briefly review the Company’s operational progress, provide an update on business activities for the third quarter of 2023, and review the latest data presented at the 2023 Annual Congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper), before taking questions from participants.

Details for the call are as follows:

Live (US): 1-888-886-7786

Live France: 0 800 916 834

Live (international): 1-416-764-8658

Call me: click here

Participants can use guest dial-in numbers above and be answered by an operator or they can click the Call me link for instant telephone access to the event (dial-out). The Call me link will be made active 15 minutes prior to scheduled start time. A live webcast of the call may be accessed by visiting the investors section of the Company’s website at www.nanobiotix.com. It is recommended to join 10 minutes prior the event start. A replay of the webcast will be available shortly after the conclusion of the call and will be archived on the Company’s website.

Participants are invited to email their questions in advance to [email protected].

On November 13, 2023 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 across its clinical development pipeline in its quarterly filing with the Securities and Exchange Commission (Press release, Moleculin, NOV 13, 2023, View Source [SID1234637553]).

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"Despite a host of recent new drug approvals, the most important therapeutic tool for treating AML and advanced STS continues to be an anthracycline. We believe the data we are now showing in Annamycin’s clinical trials on those indications are demonstrating a potential to finally bring an anthracycline to the table for those patients who have until now been prevented from using them," Walter Klemp, Chairman and Chief Executive Officer of Moleculin stated. "Importantly, as we continue to show zero cardiotoxicity in 100% of subjects in multiple studies, Annamycin is now also showing substantial activity in Phase 2 studies across two indications."

"Having 38% of subjects with a median age of 68 in our MB-106 AML study receiving a full course of Annamycin show a complete response with durability of up to approximately 8 months and counting, we believe, is exceptional while also demonstrating no cardiotoxicity," Dr. Paul Waymack, Senior Chief Medical Officer said. "Adding to this, we are showing in our Phase 1B/2 study with Annamycin treating soft tissue sarcoma (STS) with pulmonary metastases for subjects with no limit on prior therapies (median of 3; range of 1-11) PFS of 2.2 months or better for 59% of the subjects (N=32). In subjects with fewer prior therapies (prior therapies <2) and dosed with Annamycin at or below 330 mg/m2, this increased to 78% and, additionally, we are showing PFS of 3.4 months for 56% (N=9) of these subjects. Having a preliminary median of 11.3 months of overall survival once the subject has entered into our Phase 1B study (Extended OS), is exciting as these subjects were heavily pre-treated. For the overall study, we have an opportunity for the Extended OS and PFS data to get better as subjects continue to be monitored."

Ongoing Clinical Trial Updates

Next Generation Anthracycline – Annamycin

Annamycin is the Company’s next-generation anthracycline that has been designed to be non-cardiotoxic (unlike currently prescribed anthracyclines) and has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin (a commonly prescribed anthracycline and the standard of care chemotherapy for advanced STS), as well as demonstrating the ability to avoid the multidrug resistance mechanisms that typically limit the efficacy of doxorubicin and other currently prescribed anthracyclines. An independent expert evaluated the first 62 subjects in the Company’s four clinical trials and confirmed that there are no signs of cardiotoxicity. In total 66 subjects (4 are yet to be reviewed) have been treated in the Company’s clinical trials and none have shown any signs of cardiotoxicity. This includes 50 subjects treated over the lifetime maximum anthracycline dose set by the U.S. Food and Drug Administration (FDA). Annamycin is currently in development for the treatment of both first line therapy and therapy for relapsed or refractory acute myeloid leukemia (AML), as well as, STS lung metastases (STS lung mets), and the Company believes the drug may have the potential to treat additional indications.

AML

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. The Company has not treated any first line subjects to date.

Table 1 – Summary of Annamycin Responses in AML Studies

Study

Study MB-105
Monotherapy – Last
Cohort at 240
mg/m2 (RP2D)

Study MB-106
Combination Therapy –
Phase 1B
(Annamycin at 190-
230 mg/m2)

Study MB-106
Combination Therapy
– Phase 2 To Date
(Annamycin at 230
mg/m2)

Study MB-106
Combination Therapy
– Phase 1B/2 To Date
(Annamycin at 190-
230 mg/m2)

Therapy

Annamycin – Single
Agent

Ara-C + Annamycin
"5+3+

Ara-C + Annamycin
"5+3+

Ara-C + Annamycin
"5+3+

Subjects To date

5

6

2

8

CRs

0

2

1

3

CRis

3

0

0

0

Total Response(s) or
CRcs

3

2

1

3

Overall Response
(CRc) Rate

60 %

33 %

50 %

38 %

Median Prior
Therapies (Months of
Prior Therapy))

6 (N/A)

2.5 (9)

3 (6)

3 (9)

Median Age – Years
(Range)

65 (62-73)

66 (32-78)

69 (69-70)

68 (32-78)

Durability of CRs

Not followed

Approximately 8 and 3
months, respectively,
to date for the 2 CRs

Not Available at This
Time

See Data to Left

N/A (Not available)

For all subjects receiving a full course of Annamycin

Above is a table that shows a summary of the data to date for MB-106 and, for reference, the data for the last cohort in the MB-105 AML study with Annamycin as a monotherapy is shown as well. The data described and shown above is preliminary and subject to change, except for the MB-105 data where a Clinical Study Report has been completed.

MB-106 Phase 1B/2 clinical trial began dosing subjects in March 2023. Nine clinical sites in Poland and Italy have been activated for the MB-106 trial. The Company is planning for a total of up to [eleven] sites in the European Union (EU).

The median number of prior therapies for these 3 subjects in the first cohort was five (range of one to ten). One subject, who was 78 years of age at the time of the study initiation and enrolled after a single prior multi-year therapy, achieved a CR that has continued to be durable at approximately 8 months. This subject has received a second course of treatment at the direction of the treating physician and as allowed per the protocol. The other 2 subjects were shown to have disease progression. On August 7, 2023, Moleculin successfully completed the second cohort at 230 mg/m2 of Annamycin in this combination study. Four subjects were treated in this cohort, 1 is believed to be relapsed from one or more prior therapies and 3 are believed to be refractory from up to three prior therapies. One subject was replaced due to a Serious Adverse Event (SAE) experienced on Day 1 of dosing. The SAE was determined to be unrelated to Annamycin and definitively related to Cytarabine. The Company, at the recommendation of the safety review committee, deemed the second cohort dose as safe and opened recruitment, including for both first line therapy and for subjects who are refractory to or relapsed after induction therapy, to the Phase 2 portion of the trial. The median number of prior therapies for the 3 evaluable subjects in the second cohort was two (range of one to three) and the median age was 67. One subject, who was 64 years of age at the time of enrollment into the study with one prior therapy, was preliminarily recorded as a CR with an incomplete recovery of the bone marrow, or CRi, per the protocol. This has since been deemed a CR, which has shown to be durable for approximately three months, which has allowed this subject to proceed to a bone marrow transplant. The other 2 subjects were shown to have disease progression. Durability of CR’s is confirmed by and repeat bone marrow aspirates (BMA’s).

The total CRs in the Phase 1B portion of this combination trial represent 33% (n=6). Notably, these CRs are considered durable. The median age of these subjects was 66.

On October 2, 2023, Moleculin announced the initial subjects had been treated in the Phase 2 portion of MB-106. The data above is as reported by the investigation sites as of November 9, 2023.

The Company has recruited, treated, and evaluated 3 subjects in the Phase 2 portion of the trial. One subject has been evaluated and determined to be a [CR]. The Company will assess the durability in the near future. Another subject in the Phase 2 portion died from a stroke (deemed not be related to Annamycin) prior to being re-biopsied to determine disease status. The third has undergone a re-biopsy which shows zero blasts in the marrow and that data is now being assessed by the investigator. This latest subject is not included in the chart above. The median age of the first two subjects is 69 years (range of 69 to 70) and the median number of prior therapies for these subjects is three (both are three). Other subjects in the Phase 2 portion of the trial are in the process of screening and treatment. The Company intends to treat up to 21 subjects in this Phase 2 portion of the trial. The Company may recruit an additional 3 subjects depending on recruitment. At the Company’s rate of recruitment plus the addition of another three sites for the trial, Moleculin expects to complete recruitment by early 2024.

The total CRs in both Phases to date in MB-106 represent 38% (n=8), and although sufficient time has not passed to assess durability for the latest of these CRs, the 2 earlier CRs have now shown durability. The median baseline bone marrow assessments for the 3 CRs was 74.2 (range of 20 to 80).

STS Lung Mets

Table 2

MB-107 Summary as of November 9, 2023

Progression

Free Survival

Months (mos)

All

Subjects

Phase 1B

All

Subjects

Phase 2

All

Subjects

All Subjects

Treated at <

330 mg/m2

All Subjects

with 2 or Fewer

Prior Therapies

(< 2PT)

All Subjects <

330 mg/m2 &
< 2PT

1 mos or >

100 %

100 %

100 %

100 %

100 %

100 %

2 mos or >

59 %

67 %

53 %

61 %

83 %

78 %

3 mos or >

25 %

27 %

24 %

30 %

42 %

56 %

4 mos or >

16 %

13 %

18 %

22 %

25 %

33 %

5 mos or >

9 %

7 %

12 %

13 %

8 %

11 %

6 mos or >

6 %

0 %

12 %

9 %

8 %

11 %

n =

32

15

17

17

12

9

Median mos

2.2

2.6

2.0

2.1

2.7

3.4

Median Prior
Therapies
(Range)

3 (1-11)

3 (1-9)

3 (1-11)

3 (1-11)

2 (1-2)

2 (1-2)

Median O/S
mos

N/A

11.3

N/A

N/A

N/A

N/A

Overall survival (OS); Not available for Phase 2 subjects at this time, as majority of subjects continue survival (N/A)

On September 21, 2023, Moleculin announced the completion of enrollment in the Phase 2 portion of its U.S. Phase 1B/2 clinical trial evaluating Annamycin as monotherapy for the treatment of soft tissue sarcoma lung metastases (MB-107). Subjects who had stable disease at the time of study discontinuation will continue to be followed for progression free response and overall survival. All subjects had pulmonary metastasis from soft tissue sarcoma and at least one prior therapy. There was no limit on how many prior therapies a subject could have prior to entering this study. Most subjects were heavily treated with other therapies prior to entering our trial with our treatment representing the fourth median therapy for all subjects in the Phase 1B and Phase 2 portion of the trial (range of two to twelve). As of November 6, 2023 as reported by the investigation sites, most subjects in Phase 2 are alive so overall survival data is not available at this time. Above in Table 2 is a summary of progression free survival for evaluable subjects, as discussed further below, by groupings and median overall survival for all subjects evaluable in Phase 1B.

In the Phase 1B portion of the trial, subjects were treated from 210 mg/m2 to 390 mg/m2. In the Phase 2 portion of the trial, an exploratory RP2D of 360 mg/m2 was initiated for the first 3 subjects and a final RP2D of 330 mg/m2 was determined and 14 subjects were treated.

Including the 3 subjects treated at the same dose in the Phase 1B portion of this trial, this equates to 17 total subjects measurable for efficacy at the 330 mg/m2 dose level. Including all measurable subjects at all dose levels in the Phase 1B portion of the trial, 32 subjects were treated with at least one cycle in this study and 27 received at least two cycles of treatment. For these subjects, the median time to entering the MB-107 trial from the time of initial diagnosis is estimated to be approximately 20 months, and these subjects have been mostly heavily treated previously for STS lung mets prior to entering the Company’s study.

Once all data is collected, Moleculin plans to release a more in-depth presentation of the topline data for this study in 2024. The above information in Table 2 was shared with the Company’s investigators in a meeting held during the Connective Tissue Oncology Society Annual Meeting (CTOS) in Dublin, Ireland in early November 2023. Based on the data as shown in Table 2 above, Moleculin believes the following observations are in order:

Very few trials for subjects with such advanced (median = 20 months from initial diagnosis; all with lung metastases in MB-107) disease progression have been published, making comparisons to historical performance difficult.
With this in mind, median OS for subjects in the Phase 1B portion of this study is currently at 11 months, which the Company believes is notable.
Overall median Progression Free Survival (PFS) for the trial is 2.2 months (range 1.2 to 6.9 months) with 7 subjects discontinuing early due to thrombocytopenia. Five of these subjects negatively impacted this median PFS, which the Company believes was exacerbated by the extreme advanced stage of the patients and their being weakened by prior therapies.
Median PFS improved to 3.4 months for lower doses of Annamycin ( 330 mg/m2) versus the maximum dose used in the trial and for subjects who had fewer prior therapies (<2).
These data suggest to us that Annamycin may be best positioned as a first line alternative to the current standard of care with an anthracycline and where the combination of high patient response rate, significant improvement in OS and the absence of cardiotoxicity may improve patient outcomes.
All data presented above from the MB-107 trial are preliminary and subject to change.

Expected Upcoming Annamycin Milestones

AML
In-depth data review and presentation of topline data on MB-106 clinical trial.
MB-106 End of Phase 2 (EOP2) Meeting.
Identify next phase of development / pivotal program.
Initiate pivotal program.
STS Lung Mets
Final MB-107 data readout.
Identify next phase of development / pivotal program.
Initiate first line study STS.
Flagship Immune/Transcription Modulator – WP1066

Moleculin is in ongoing discussions with multiple academic institutions in separate programs evaluating WP1066 for the treatment of glioblastomas and/or pediatric brain tumors. The Company expects to finalize agreements with Northwestern University and FDA filings in the early 2024 (Clinicaltrials.gov ID: NCT05879250).

Recent Activity Highlights

Ongoing progress in development of an intravenous formula for WP1066.
The Company supplied drug product to an externally funded pediatric brain tumor trial with WP1066 up to its conclusion in February 2023 and expects additional externally funded clinically trials for WP1066 (in combination with radiation) in 2023 in the U.S. and, possibly, in Southeast Asia.
Expected Upcoming Milestones

Report topline results from investigator-initiated Phase 1 study in pediatric brain tumors.
Seek external funding opportunities for an investigator-initiated clinical trial in adult and pediatric cancer patients in 2023.
Announce progress regarding an IV formulation by the end of 2023 or in early 2024.
Metabolism/Glycosylation Inhibitor – WP1122 Portfolio

WP1122 was developed as a prodrug of 2 deoxy-D-Glucose (2-DG) to provide a more favorable pharmacological profile and was found to have greater potency than 2-DG monotherapy in preclinical models where tumor cells require higher glycolytic activity than normal cells. WP1122 has also been shown to have a greater antiviral effect than 2-DG against SARS-CoV-2 in MRC-5 cells in culture. The improved pharmacokinetic and pharmacodynamic (PK/PD) profile of WP1122 compared to 2-DG was noted in mice following oral dosing at equimolar (i.e., equivalent levels of 2-DG) doses. The WP1122 Portfolio includes numerous analogs, including WP1096, which has demonstrated the potential for broad antiviral capabilities in a wide range of in vitro models including multiple arenaviruses, filoviruses, Zika virus, and HIV. The Company looks forward to the potential of additional externally funded research to confirm such activity.

Expected Upcoming Milestones

Report preliminary findings of National Institutes of Health (NIH) funded animal testing of WP1096 in the Tacaribe Arenavirus.
Identify investigators interested in initiating a clinical trial to study the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM.
General Information on the Company’s Core Technologies

Annamycin currently has Fast Track Status (FTS) and Orphan Drug Designation (ODD) from the FDA for the treatment of soft tissue sarcoma, in addition to ODD for the treatment of acute myeloid leukemia. WP1066 has ODD for the treatment of GBM and has four indications designated for the FDA Rare Pediatric Disease Priority Review Voucher (PRV) Program. WP1122 has ODD and FTS for GBM, as well. For more information about the Company’s trials, please visit clinicaltrials.gov.

On November 13, 2023 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a growing pipeline, including Phase 2 clinical programs, for hard-to-treat tumors and viruses, reported its financial results for the quarter ended September 30, 2023 (Press release, Moleculin, NOV 13, 2023, View Source [SID1234637552]). As previously announced, the Company will host a conference call and live audio webcast, today, November 13, 2023, at 8:30 AM ET (details below).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"There remains a dire unmet need in AML and STS for a safer, non-cardiotoxic chemotherapy for elderly and frail patients," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. "Our growing body of positive clinical and encouraging safety data for Annamycin continues to bolster our confidence that our next generation chemotherapy can make a significant impact in the treatment landscape for these high value indications. We remain focused on advancing our priority pipeline programs to key data milestones in the near term, which we be believe will support advancement into pivotal, registration studies in both AML and STS. We believe our year of continued data and the achievement of clinical and regulatory milestones will translate into significant value creation for all of our stakeholders."

Recent Highlights

Dosed first subjects in Phase 2 portion of the clinical trial evaluating Annamycin in combination with Cytarabine (Ara-C) for the treatment of Acute Myeloid Leukemia (AML) (MB106);
Completed enrollment in U.S. Phase 1B/2 clinical trial evaluating Annamycin for the treatment of Soft Tissue Sarcoma (STS) Lung Metastases (MB107);
Announced a new positive independent assessment report was published confirming the absence of cardiotoxicity in subjects treated with Annamycin;
Presented poster titled, "A Phase 1b/2 Study of Liposomal Annamycin (ANN) in Subjects with Previously Treated Soft-Tissue Sarcomas (STS) with Pulmonary Metastases" at the 2023 Connective Tissue Oncology Society Annual Meeting in Dublin, Ireland;
Participated in the Virtual Investor Ask the CEO Conference, the webcast replay can be found here; and
The Company will release a more detailed Clinical Trial Update press release later this morning.
Summary of Financial Results for the Third Quarter 2023

Research and development (R&D) expense was $3.3 million and $6.0 million for the three months ended September 30, 2023 and 2022, respectively. The decrease of $2.7 million is mainly related to the timing of costs incurred for clinical trials and timing of sponsored research payments.

General and administrative expense was $2.6 million and $3.1 million for the three months ended September 30, 2023 and 2022, respectively. The decrease of $0.5 million is mainly related to a decrease in regulatory and legal services, and consulting & advisory fees.

As of September 30, 2023, the Company had cash and cash equivalents of $24.6 million and believes that this cash is sufficient to meet its planned operations, which include the current Phase 2 clinical programs and preparations for future clinical trials, into the third quarter of 2024.

Conference Call and Webcast

Moleculin management will host its quarterly conference call and webcast for investors, analysts, and other interested parties today, November 13, 2023, 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 November 13, 2023 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies ("ETBs"), to create novel therapies with potent differentiated mechanisms of action for cancer, reported financial results and business updates for the third quarter of 2023 (Press release, Molecular Templates, NOV 13, 2023, View Source [SID1234637551]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Eric Poma, PhD., Chief Executive and Chief Scientific Officer of MTEM, stated, "ETBs represent a new approach to oncology drug development that continue to show unique biology and monotherapy activity in heavily pre-treated patients. We expect to see substantial additional data across all three of our clinical programs with updates throughout this year and into 2024."

Company Highlights

Initiation of expansion study with MT-6402 (PD-L1) exploring 63 and 83 mcg/kg doses; compelling early evidence of monotherapy activity in patients with relapsed or refractory Head and Neck cancer observed at the 63 and 83 mcg/kg doses observed
First patient dosed in phase I study for MT-8421 targeting CTLA-4-expressing regulatory T-cells ("Tregs") in the tumor microenvironment ("TME") for elimination without affecting peripheral Tregs
MT-0169 (CD38): The company is in the process of declaring the recommended doses that will be further investigated in CD38+ malignancies.
Clinical data for each program continues to demonstrate novel mechanisms of action, unique pharmacodynamic ("PD") effects, and single agent activity in heavily relapsed/refractory patients across immuno-oncology, hematologic, and solid tumor indications observed
No instances of capillary leak syndrome ("CLS") or other manifestations of innate immunity have been observed to date with any next-generation ETB
Focus on preclinical activities related to Bristol Myers Squibb collaboration moves forward
MT-6402 (PD-L1 ETB)

The Part A dose escalation of the phase I for MT-6402 has been completed with no Grade 4 or Grade 5 drug-related adverse events having been observed to date.

In the Part A dose escalation, 10 patients with head and neck cancer were treated at doses of 63, 83, or 100 mcg/kg. Two of these patients were not evaluable for the cycle 1 dose-limiting toxicity ("DLT") period because of early progression and came off study after receiving only one or two doses of MT-6402, respectively. Of the remaining eight head and neck cancer patients, the best responses observed were as follows: two had a partial response (one unconfirmed), and a third patient had evidence of tumor regression. All three patients had progressed after multiple lines of treatment including checkpoint therapy. The unconfirmed partial response was in a patient who was pembrolizumab-refractory.

Three other patients had stable disease of 6, 4, and 2 months, respectively, before disease progression or discontinuation. A fourth patient remains in stable disease at cycle 5. One patient progressed at the end of cycle 2. Of these 8 patients, only one patient (the patient with stable disease through 6 cycles) had a PD-L1 tumor proportion score ("TPS") greater than 50%.

"We are very excited to see responses in heavily pre-treated, checkpoint-experienced, head and neck cancer patients, a setting with high unmet medical need," said Eric Poma. "The TME in head and neck tumors is typically rich with immunosuppressive cells, but current checkpoint monotherapy in I/O-naïve head and neck patients has a ~15% response rate. Here, in patients who have progressed on checkpoint therapy, we believe we are seeing evidence of monotherapy activity of long duration and monotherapy activity in a patient refractory to checkpoint therapy. The responses observed to date were in patients with CPS <20% and showed concomitant increases in cytokines associated with T-cell activation that are not seen with other checkpoint therapies. We believe these data demonstrate a new and potentially best-in-class approach to targeting the PD-1-PD-L1 axis."

"MT-6402 appears generally well-tolerated at the 63 and 83 mcg/kg doses with no Grade 4 or Grade 5 adverse events and no instances of CLS seen at any dose," said Dr. Maurizio Voi, Chief Medical Officer of Molecular Templates. "The irAE profile of MT-6402 appears to be consistent with that seen with other checkpoint therapies."

The Part B dose expansion is ongoing, with three patients currently on treatment but not yet evaluable for efficacy. The 63 and 83 mcg/kg doses will be studied in the expansion cohort in patients with >50% tumor expression of PD-L1, allowing for the potential of direct tumor cell-kill. Additionally, in patients with the HLA-A*02 haplotype and who are CMV+, the antigen seeding mechanism of MT-6402 may be engaged.

MT-8421 (CTLA-4 ETB)

MT-8421, along with MT-6402, represent our unique approach to immuno-oncology based on dismantling the TME through, and the elimination of, immunosuppressive cells in the TME.
MT-8421 is designed to potently destroy CTLA4+ Tregs via enzymatic ribosome destruction but does not have activity against low CTLA-4 expressing peripheral Tregs.
Clinical sites are open and enrollment has commenced on this program.
MT-0169 (CD38 ETB)

MT-0169 was designed to destroy CD38+ tumor cells through internalization of CD38 and cell destruction via a novel mechanism of action (enzymatic ribosomal destruction and immunogenic cell death).
MT-0169 will continue to be studied in CD38 hematological malignancies. No adverse events ≥ Grade 3 have been observed.
One patient with extra medullary IgA myeloma treated at 5 mcg/kg has had a marked reduction in IgA serum protein, conversion from immunofixation positive to negative and resolution of uptake on bone scan of skeletal lesions demonstrating a stringent Complete Response.
The patient’s disease was quad-agent refractory, including CD38-targeting antibody, proteosome inhibitor, IMiD, and a BCMA bispecific antibody.
The patient continues on study in a response at cycle 16.
Research and Collaboration

MTEM continues to make progress in the drug discovery collaboration with Bristol Myers Squibb.
Key Upcoming Milestones

Accelerating enrollment across all clinical programs.
Advancement of Bristol Myers Squibb research collaboration across multiple targets. Under terms of the agreement, Molecular Templates received $70M upfront and will undertake research responsibilities for the discovery of next-generation ETBs for multiple undisclosed targets.
MTEM expects to provide a year-end update and periodic updates on MT-6402, MT-8421, and MT-0169 throughout 2024.
Upcoming Conferences

Stifel Annual Health Care Conference

Format: Live Presentation and One-on-One Meetings
Date: Wednesday, November 15, 2023
Time: 10:55 am Eastern Time
Location: Lotte New York Palace Hotel, New York, NY
Webcast: The live-streamed webcast can be accessed here
Meetings: To be scheduled by contact with Stifel representative
The presentation link will be archived for 90 days here in the "News and Media" section of the corporate website.

Evercore ISI 6th Annual HealthCONx Conference

Format: One-on-one meetings
Dates: November 28 – 30, 2023
Location: Kimpton Epic Hotel, Miami, FL
Meetings: To be scheduled directly with Molecular Templates
Financial Results

The net loss attributable to common shareholders for the third quarter of 2023 was $4.2 million, or $0.82 per basic share and per diluted share. This compares with a net loss attributable to common shareholders of $24.6 million, or $6.56 per basic and diluted share, for the same period in 2022.

Revenues for the third quarter of 2023 were $6.8 million, compared to $4.2 million for the same period in 2022. Revenues for the third quarter of 2023 were comprised of revenues from the collaborative research and development agreement with Bristol Myers Squibb and grant revenue from CPRIT.

Total research and development expenses for the third quarter of 2023 were $7.6 million, compared with $22.0 million for the same period in 2022. Total general and administrative expenses for the third quarter of 2023 were $4.3 million, compared with $5.9 million for the same period in 2022.

As of September 30, 2023, MTEM’s cash and cash equivalents totaled $15.8 million. MTEM anticipates cash runway to the end of the second quarter of 2024.

On November 13, 2023 mAbxience, a Fresenius Kabi majority-owned group with partial ownership from Insud Pharma, reported an exclusive licensing agreement with MS Pharma to commercialize the Denosumab biosimilar in select MEA markets (Press release, mAbxience, NOV 13, 2023, View Source [SID1234637549]). Denosumab is a monoclonal antibody drug that inhibits bone resorption. It is indicated for two major therapy categories: bone metastasis from various cancer forms and prevention of bone pain and fractures, including osteoporosis-related injuries.

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Under the agreement’s terms, mAbxience will conduct the full development of the biosimilar and manufacture it in its state-of-the-art, Good Manufacturing Practice (GMP) approved facilities, while MS Pharma will guide the products through regulatory approval and have exclusive commercialization rights in select MEA Countries. The financial terms of the transaction were not disclosed.

This partnership signifies a deeper collaboration between mAbxience and MS Pharma, building upon their previous licensing agreements with bevacizumab and rituximab and further advancing their shared mission to enhance global health. "We are excited to further solidify our relationship with MS Pharma through this new agreement. This collaboration will introduce a world-class biosimilar for bone diseases and oncology treatment to patients across the MEA region, underscoring our commitment to ensuring global access to high-quality, life-enhancing treatments. In tandem with MS Pharma, we are steadfast in our dedication to offering affordable and accessible healthcare solutions, positively impacting public health, and fortifying our position in the global biosimilar space," said Emmanuelle Lepine, CEO of mAbxience.

Kalle Känd, CEO at MS Pharma, said: "This agreement marks a significant milestone in MS Pharma’s journey to becoming a frontrunner in the specialized field of biosimilars. Our partnership with mAbxience underscores our mutual quest to enhance patient care by providing advanced therapeutic options that are effective, accessible, and affordable. By bringing the Denosumab biosimilar to MEA markets, we are addressing a critical healthcare void in both bone diseases and oncology treatment and delivering on our promise of better health for all."

The MEA region faces significant health challenges related to both cancer and bone diseases. Denosumab, a monoclonal antibody drug, is crucial in this context as it inhibits bone reabsorption and is indicated for bone metastasis from various cancer forms. Within the MEA region, the prevalence of low bone mass stands out as being notably higher than in western countries, emphasizing the urgent need for interventions and treatments. Alarmingly, despite abundant sunlight, the MEA region registers the highest global rates of rickets. The high prevalence of hypovitaminosis D, which could be a contributing factor to osteoporosis, is also a significant concern. Furthermore, post-hip fracture mortality rates are dauntingly high, being 2-3 times greater than those in western nations. These factors, combined with the rising incidence of cancer, underscore the essential need for comprehensive healthcare solutions, treatments, and interventions tailored to the region’s unique challenges.