On November 10, 2022 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported its financial results for the quarter ended September 30, 2022 and provided a pipeline update (Press release, Moleculin, NOV 10, 2022, View Source [SID1234623714]). As previously announced, the Company will host its inaugural quarterly conference call and live audio webcast, today, November 10, 2022, at 5:00 PM ET (details below).

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"We have made fundamental progress across our pipeline this past quarter. Of note, we have three active Phase 1/2 clinical trials for Annamycin and patients treated thus far continue to demonstrate no evidence of cardiotoxicity. Additionally, we have gained valuable insight in all of our ongoing development programs and are well-positioned to successfully execute operationally through the remainder of the year. Looking ahead, as we continue delivering on our initiatives, I believe the fourth quarter is poised to be an exciting conclusion of a transformational year and foundational for what is to come," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin.

Recent Highlights

Opened enrollment in the Phase 1/2 Study of Annamycin in combination with cytarabine for the treatment of Acute Myeloid Leukemia ("AML") in Europe.
Initiated and began dosing in the Phase 2 portion of the U.S. Phase 1b/2 clinical trial evaluating Annamycin for the treatment of soft tissue sarcoma lung metastases ("STS lung mets").
An investigator-funded, second Phase 1b/2 clinical trial of Annamycin in STS lung mets in Europe was commenced and began dosing.
Continued expanding the safety profile of Annamycin with a third report from an independent cardiology expert assessing recent subjects. This assessment again confirmed that there was no evidence of cardiotoxicity associated with Annamycin. This brings the total to 42 subjects where no evidence of cardiotoxicity has been identified by an independent expert cardiologist.
Enrolled what is expected to be the final subject in the Phase 1 portion of a clinical trial of WP1066 being conducted in collaboration with Emory University for the treatment of pediatric brain tumors, including medulloblastoma and diffuse interstitial pontine glioma ("DIPG").
Concluded Phase 1a first-in-human clinical trial of WP1122 for the treatment of COVID-19 in the United Kingdom establishing a safe and tolerable dose in healthy volunteers.
Announced the selection of WP1096 (a compound in the WP1122 portfolio) as novel potential antiviral, by the National Institute of Allergy and Infectious Diseases ("NIAID"), part of the National Institutes of Health ("NIH"), for NIH-funded animal studies.
Received U.S. Food and Drug Administration ("FDA") Orphan Drug Designation of WP1122 for the treatment of Glioblastoma Multiforme ("GBM").
Pipeline Update

Next Generation Anthracycline – Annamycin

Annamycin is the Company’s next-generation anthracycline that has been designed to be non-cardiotoxic 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), as well as demonstrating the ability to avoid the multidrug resistance mechanisms that typically limit the efficacy of doxorubicin and other currently prescribed anthracyclines. Annamycin is currently in development for the treatment of relapsed or refractory AML and STS lung metastases and the Company believes it may have the potential to treat additional indications.

STS Lung Mets

The Company recently initiated its Phase 2 portion of the U.S. Phase 1b/2 clinical trial evaluating Annamycin for the treatment of STS lung mets ("MB-107") and has begun enrollment and dosing.

In the Phase 1b portion of the study, 15 subjects were enrolled and treated per the protocol in four cohorts to determine the maximum tolerable dose and/or the RP2D. Each cohort had three subjects, except for the fourth cohort, which (per the protocol) was expanded to six subjects after a dose-limiting toxicity (DLT) occurred in a single subject. The Company concluded the Phase 1b portion after the fourth cohort of 390 mg/m2 was documented to be safe. Based on findings from the Phase 1b position of the trial, 360 mg/m2 demonstrated it may be tolerated by subjects initially, however continued treatment was deemed at risk to be delayed or interrupted due to adverse events (primarily myelosuppression, which is anticipated with high doses of anthracycline therapy), hence lowering the dose from 360 mg/m2 to 330 mg/m2 was contemplated in advance of beginning the Phase 2 expansion pending results from the first three subjects in the expansion phase. Adverse Events, primarily myelosuppression, in the first three subjects at 360 mg/m2 led the Company to lower the RP2D to 330 mg/m2 in October 2022, which the Company believes will enable continued treatment of subjects with fewer interruptions.

The Company expects to treat at least 25 subjects in this Phase 2 portion of the clinical trial. For more information about the Phase 1b/2 study evaluating Annamycin for the treatment of STS lung mets, please visit clinicaltrials.gov and reference identifier NCT04887298.

Additionally, the investigator-funded, second Phase 1/2b clinical trial of Annamycin for the treatment of STS lung mets was recently initiated. The grant-funded clinical trial is being led by Prof. Piotr Rutkowski, MD, PhD, Head of Department of Soft Tissue/Bone Sarcoma and Melanoma at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland. The trial will use a dosing regimen of once weekly for three weeks in a 28-day cycle rather than once every 21 days as in the US trial. Two subjects have been dosed to date.

AML

Patient enrollment and screening has been initiated in the Company’s Phase 1/2 clinical trial in Poland 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 who are refractory to or relapsed after induction therapy ("MB-106"). Ongoing efforts to open additional clinical sites in Poland and other European countries for the MB-106 clinical trial are underway.

Annamycin currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of STS lung metastases, in addition to Orphan Drug and Fast Track Designation for the treatment of relapsed or refractory AML.

Upcoming Milestones Expectations

Q4 2022: Commence dosing and open additional clinical sites in Poland and other European countries in the Phase 1/2 study of Annamycin in combination with Ara-C in Acute Myeloid Leukemia.
Q1 2023: Report Phase 2 interim data from ongoing Phase 1b/2 study of Annamycin for the treatment of STS lung mets in the US and Europe.
Flagship Immune/Transcription Modulator – WP1066

WP1066 is designed to stimulate the immune response to tumors by inhibiting the errant activity of Regulatory T-Cells (Tregs) while also inhibiting key oncogenic transcription factors, including p-STAT3 (phosphorylated signal transducer and activator of transcription 3), c-Myc (a cellular signal transducer named after a homologous avian virus called Myelocytomatosis) and HIF-1α (hypoxia inducible factor 1α). These transcription factors are widely sought targets that are believed to contribute to an increase in cell survival and proliferation, and the angiogenesis (coopting vasculature for blood supply), invasion, metastasis and inflammation associated with tumors. They may also play a role in the inability of immune checkpoint inhibitors to affect more resistant tumors.

Moleculin is in ongoing discussions with multiple academic institutions in separate programs evaluating WP1066 for the treatment of brain tumors. The Company expects the investigator-sponsored clinical trials or programs for the treatment of adult and pediatric brain tumor to commence in the first half of 2023.

Additionally, WP1066 is currently being evaluated in collaboration with Emory University for the treatment of pediatric brain tumors, including medulloblastoma and DIPG. In October 2022, the Emory trial enrolled the last subject in the last cohort at 8 mg/kg. Discussions are underway to explore WP1066 in combination with radiation on similar tumors in a Phase 2 clinical trial in the near future.

In April 2022, the Company received IND clearance from the FDA to conduct a Phase 1 study of WP1066 for the treatment of recurrent malignant glioma. Since that time, the Company has been evaluating strategic partnerships and collaborations to utilize this IND. WP1066 has received Orphan Drug Designation for the treatment of brain tumors, as well as Rare Pediatric Disease designation for three other pediatric indications. Additionally, WP1066 + radiation is being evaluated, pre-clinically, in the treatment of Glioblastoma Multiforme (GBM).

Upcoming Milestones Expectations

H1 2023: Commencement of investigator-sponsored clinical trials or programs for the treatment of adult and pediatric brain tumors.
Metabolism/Glycosylation Inhibitor – WP1122 Portfolio

WP1122 was developed as a 2-DG prodrug to provide a more favorable pharmacological profile and was found to have greater potency than 2-DG alone 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, Zika virus, and HIV.

Glioblastoma Multiforme

In September of 2022, Moleculin was granted Orphan Drug Designation of WP1122 for the treatment of GBM from the FDA. Additionally, based on preclinical data indicating the potential for WP1122 as a treatment for GBM, Moleculin received FDA clearance of its Investigational New Drug application to initiate a Phase 1 open label, single arm, dose escalation study of the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM. The Company is currently evaluating opportunities for collaboration in clinical development.

COVID-19

In October 2022, the Company concluded its Phase 1a, first-in-human, randomized, double-blind, placebo-controlled, overlapping SAD and MAD clinical trial investigating the effects of WP1122 administered as an oral solution in healthy human volunteers. A safe and tolerable dose was established for WP1122 in this trial, which now provides a starting point for a range of potential Phase 2 clinical trials. Approximately 80 subjects were enrolled in the trial.

Upcoming Milestones Expectations

Identify investigators interested in initiating a Phase 1 open label, single arm, dose escalation study of the safety, pharmacokinetics and efficacy of oral WP1122 in adult patients with GBM.
Report preliminary findings of NIH-funded animal testing of WP1096 in the Tacaribe Arenavirus by the end of the first quarter 2023.
Summary of Financial Results for the Third Quarter 2022

Research and development (R&D) expense was $14.8 million and $11.2 million for the nine months ended September 30, 2022 and 2021, respectively. The increase of $3.6 million is mainly related to increased clinical trial activity as described above, a license termination fee, and costs related to manufacturing of additional drug product.

General and administrative expense was $8.7 million and $6.4 million for the nine months ended September 30, 2022 and 2021, respectively. The increase of $2.3 million is mainly related to an increase in regulatory and legal services, consulting and advisory fees.

For the nine months ended September 30, 2022 and 2021, the Company incurred net losses of $22.3 million and $13.1 million, respectively, and had net cash flows used in operating activities of $20.4 million and $14.7 million, respectively.

The Company ended the quarter with $50.4 million of cash. The Company believes that this cash is sufficient to meet its projected operating requirements, which include a forecasted increase over its current R&D rate of expenditures, beyond mid-2024.

Conference Call and Webcast

Moleculin management will host its inaugural quarterly conference call and live audio webcast for investors, analysts, and other interested parties today, Thursday, November 10, 2022, at 5:00 PM 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 10, 2022 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing breakthrough treatments for immune-mediated and oncologic disorders, reported financial results for the third quarter ended September 30, 2022 and provided a business update (Press release, Kezar Life Sciences, NOV 10, 2022, View Source [SID1234623713]).

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"In the third quarter, the team at Kezar continued its tradition of strong execution across our clinical and portfolio development plans," said John Fowler, Kezar’s Co-founder and Chief Executive Officer. "Supported by the results from the MISSION study, our conviction remains high that zetomipzomib has the potential to be a non-immunosuppressive, steroid-sparing treatment for patients with lupus and lupus nephritis. In addition, our recently announced development plan in autoimmune hepatitis underscores our belief that zetomipzomib can help patients across a diverse range of autoimmune diseases. In parallel, we are excited by progress in our protein secretion inhibition platform and look forward to our SITC (Free SITC Whitepaper) poster presentation tomorrow on KZR-540, an oral small molecule that selectively blocks PD-1 expression."

Zetomipzomib: Selective Immunoproteasome Inhibitor

MISSION – Phase 2 clinical trial of zetomipzomib in patients with active lupus nephritis (LN) (NCT03393013)

Kezar presented positive complete results for the 37-week Phase 2 MISSION clinical trial at the American Society of Nephrology’s (ASN) Kidney Week 2022 Annual Meeting.
During the 24-week treatment period, patients received 60 mg of zetomipzomib subcutaneously once weekly (first dose of 30 mg) in addition to stable background therapy. End-of-treatment assessments occurred at Week 25 (EOT), with a safety follow up period and completion of the study at Week 37 (EOS). Patients in the MISSION Phase 2 clinical trial received zetomipzomib without induction therapy, which represents a difference from other recently published clinical trials in LN. The primary efficacy endpoint for the trial was the proportion of patients achieving an overall renal response (ORR), measured as a 50% or greater reduction in urine protein to creatinine ratio (UPCR) at end-of-treatment. A key secondary efficacy endpoint was the number of patients with a complete renal response (CRR), measured as an absolute reduction in proteinuria values to a UPCR of 0.5 or less, with preserved renal function (eGFR), and corticosteroid use of 10 mg or less prednisone/prednisone equivalent and no use of prohibited medication.
In the MISSION Phase 2 clinical trial, 17 of 21 enrolled patients reached end-of-treatment at Week 25 and end-of-study at Week 37:
ORRs were achieved in 11 of 17 patients (64.7%) at EOT. This benefit occurred with a 53% mean reduction of background corticosteroid use.
During the safety follow up period, clinical responses deepened, and ORRs increased to 16 patients (94.1%) at Week 29 and 15 patients (88.2%) at EOS. Of these responders, 12 patients (70.6%) also reached a UPCR of 0.7 or less at EOS.
CRRs were achieved in 6 of 17 patients (35.3%) at EOT, including a UPCR of 0.5 or less, stable eGFR, daily prednisone/prednisone equivalent dose of 10 mg or less, and no use of prohibited medication.
During the safety follow up period, an additional patient achieved a CRR, with the total CRRs increasing to 7 patients (41.2%) at both Week 29 and EOS.
Key measurements of SLE disease activity were reduced and key biomarkers of SLE improved. There was no evidence of early rebound of inflammation following discontinuation of zetomipzomib.
Kezar will also present the complete MISSION data set at the upcoming American College of Rheumatology (ACR) Convergence 2022, which is taking place November 10 – 14, 2022 in Philadelphia, PA. The ACR poster presentation details are available here.
PORTOLA – Phase 2 clinical trial of zetomipzomib in patients with autoimmune hepatitis (AIH) who have not benefited from standard-of-care treatment (NCT05569759)

In October 2022, Kezar received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration for zetomipzomib for the treatment of AIH. AIH is a rare, chronic disease in which the immune system attacks the liver and causes inflammation and tissue damage, severely impacting patients’ physical health and quality of life.
The PORTOLA trial (KZR-616-208) is a randomized, double-blind, placebo-controlled Phase 2a clinical trial evaluating the safety and efficacy of zetomipzomib in patients with AIH that are insufficiently responding to standard of care or have relapsed. The target enrollment will be 24 patients, who will be randomly assigned (2:1) to receive either zetomipzomib or placebo in addition to background corticosteroid therapy for 24 weeks and includes a protocol-mandated steroid taper by Week 14. The primary efficacy endpoint will measure the proportion of patients who achieve a complete response measured as normalization of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels with a successful corticosteroid taper by Week 24.
Protein Secretion Inhibition

KZR-261-101 – Phase 1 clinical trial of KZR-261 in patients with locally advanced or metastatic solid malignancies (NCT05047536)

KZR-261 is a novel, broad-spectrum agent that acts through direct interaction and inhibition of the Sec61 translocon. In preclinical studies, KZR-261 has been shown to induce a direct anti-tumor effect as well as modulate the tumor microenvironment, including enhancing anti-tumor immune responses.
The Phase 1 clinical trial of KZR-261 is being conducted in two parts: dose escalation, and dose expansion in subjects with selected tumor types. The trial is designed to evaluate safety and tolerability, pharmacokinetics and pharmacodynamics, as well as to explore the preliminary anti-tumor activity of KZR-261 in patients with locally advanced or metastatic disease.
KZR-540 – Kezar will introduce promising preclinical data on KZR-540, an oral small molecule inhibitor that selectively blocks PD-1 expression via inhibition of the Sec61 translocon, on November 11, 2022 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting in Boston, MA. KZR-540 illustrates that the Sec61 translocon can be selectively inhibited for specific anti-tumor effects and validates Sec61 inhibition as a platform for additional new chemical entities.

Details for the SITC (Free SITC Whitepaper) poster presentation are as follows:
Title: KZR-540 is a novel oral small molecule inhibitor of Sec61 cotranslational translocation that potently and selectively blocks PD-1 expression (#422)
Category: Checkpoint Blockade Therapy
Date/Time: November 11, 2022 from 9 AM – 8:30 PM ET
Presenter: Cristina Delgado-Martin, Senior Scientist, Biology
Financial Results

Cash, cash equivalents and marketable securities totaled $290.4 million as of September 30, 2022, compared to $208.4 million as of December 31, 2021. The increase was primarily attributable to net proceeds from the issuance of common stock under the "at-the-market" Sales Agreement with Cowen and Company, LLC, net of cash used in operations to advance clinical-stage programs and preclinical research and development.
Research and development expenses for the third quarter of 2022 increased by $3.4 million to $13.9 million compared to $10.5 million in the third quarter of 2021. This increase was primarily due to an increase in personnel-related expenses including non-cash stock-based compensation because of headcount growth, and higher research and clinical development expenses, to advance the zetomipzomib clinical programs and the KZR-261 Phase 1 clinical trial.
General and administrative expenses for the third quarter of 2022 increased by $1.0 million to $5.0 million compared to $4.0 million in the third quarter of 2021. The increase was primarily due to an increase in personnel-related expenses including non-cash stock-based compensation.
Net loss for the third quarter of 2022 was $17.8 million, or $0.25 per basic and diluted common share, compared to a net loss of $14.5 million, or $0.28 per basic and diluted common share, for the third quarter of 2021.
Total shares of common stock outstanding were 68.4 million shares as of September 30, 2022. Additionally, there were outstanding pre-funded warrants to purchase 3.8 million shares of common stock at an exercise price of $0.001 per share, 0.4 million outstanding restricted stock units and options to purchase 9.6 million shares of common stock at a weighted-average exercise price of $8.12 per share as of September 30, 2022.

On November 10, 2022 Panbela Therapeutics, Inc. (Nasdaq: PBLA) , a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported that financial results for the quarter ended September 30, 2022 (Press release, Panbela Therapeutics, NOV 10, 2022, View Source [SID1234623712]). Management is hosting an earnings conference call today at 4:30 p.m. ET.

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The third quarter was marked by meaningful progress.

Q3 and early Q4 Highlights:

First Patient Enrolled in the company’s Aspire Trial, Panbela’s clinical trial in the first-line treatment of metastatic pancreatic cancer.
Announced Regulatory approval for the opening of Aspire Trial sites in Spain, France and Italy.
Received approval from the Australian Human Research Ethics Committee (HREC) to expand the Aspire Trial to Australia.
Poster presentation highlighting the results for ivospemin (SBP-101) as a polyamine metabolism modulator in ovarian cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in April 2022.
Completed registered public offering totaling gross proceeds of $6 Million.
"During Q3 we advanced our pipeline, which is largely funded through partnerships and targets an approximate $5 billion total addressable market," said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. "Milestones achieved included first patient enrolled in our Aspire global trial for metastatic pancreatic cancer, approval to expand the trial into Australia and approval to open sites in Spain, France and Italy. Through our acquisition of Cancer Prevention Pharmaceuticals (CPP) and organic operational advancements, we have programs spanning pre-clinical to registration studies, including a lead asset with a fully funded registration trial scheduled to begin mid- 2023. Additionally, we bolstered our balance sheet with gross proceeds from a public offering of approximately $6.0 million. In 2023, we anticipate a consistent stream of milestones to drive shareholder value."

During Q4 2022, we expect the initiation of a Phase I/II program in STK11 mutant non-small cell lung cancer which will be our first clinical proof of concept study evaluating polyamine modulation to improve anti-PD-1 efficacy.

Looking ahead to early 2023, we expect to announce the final data from our Phase I untreated metastatic pancreatic cancer study as well as the Phase I data from the recent onset type I diabetes program. We will also be opening a neoadjuvant pancreatic cancer investigator-initiated trial with ivospemin (SBP-101) and a Phase II study in recent onset type I diabetes which is supported by Indiana University and the Juvenile Diabetes Research Foundation (JDRF).

Third quarter ended September 30, 2022 Financial Results

General and administrative expenses were $1.3 million in the third quarter of 2022, compared to $0.9 million in the third quarter of 2021. The change is due to slightly higher professional services cost as the Company continues to integrate CPP into its operations.

Research and development expenses were $2.3 million in the third quarter of 2022 compared to $1.3 million in the third quarter of 2021. The increase relates to an increase in spending on our clinical studies.

Net loss in the third quarter of 2022 was $4.4 million, or $0.21per diluted share, compared to a net loss of $2.1 million, or $0.16 per diluted share, in the third quarter of 2021.

Total cash was $0.9 million as of September 30, 2022. Total current assets were $1.8million and current liabilities were $8.0 million as of the same date. Also at September 30, 2022, total noncurrent assets, consisting of cash deposits held by our contract research organization, were $3.1million. Notes payable, plus accrued interest, on the balance sheet, the result of the acquisition of CPP, totaled approximately $7.0 million. The current portion of the notes payable plus accrued interest totaled approximately $1.8 million.

Conference Call Information

To participate in this event, dial approximately 5 to 10 minutes before the beginning of the call.

About our Pipeline

The pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention and ovarian cancer. The combined development programs have a steady cadence of news flow with programs ranging from pre-clinical to registration studies.

SBP-101

SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. The molecule has shown signals of tumor growth inhibition in clinical studies of US and Australian metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months which is final, and an objective response rate (ORR) of 48%, both exceeding what is seen typically with the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, SBP-101 has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the current Panbela sponsored clinical trial provides support for continued evaluation of SBP-101 in a randomized clinical trial. For more information, please visit View Source

Flynpovi

Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism of action inhibiting polyamine synthesis and increasing polyamine export and catabolism. In a Phase III clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. In our Phase III trial focusing on FAP patients with lower gastrointestinal tract anatomy (patients with an intact colon, retained rectum or surgical pouch) comparing Flynpovi to single agent eflornithine and single agent sulindac, Flynpovi showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI group for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP.

CPP-1X

CPP-1X (eflornithine) is being developed as a single agent tablet or high dose power sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase I or Phase II investigator-initiated trials suggest that CPP-1X treatment is well tolerated and has potential activity.

On November 10, 2022 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a clinical-stage precision oncology company, reported financial results for the quarter ended September 30, 2022, and recent corporate updates (Press release, Kinnate Biopharma, NOV 10, 2022, View Source [SID1234623711]).

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"We continue to make advances with our proprietary programs, and are encouraged by what we’re seeing thus far in the ongoing dose escalation for KIN-2787 monotherapy, our pan-RAF inhibitor," said Nima Farzan, chief executive officer, Kinnate Biopharma Inc. "We are actively investigating multiple targets as part of the Kinnate Discovery Engine and look forward to having a third program enter the clinic next year. We remain well funded to continue to innovate and progress our pipeline of novel small molecule drug candidates."

Pipeline Updates

Announced an update from the ongoing dose escalation for KIN-2787 monotherapy in the global Phase 1 clinical trial, KN-8701. Detailed dose escalation data is expected in the first half of 2023. (View Release)
Subsequent to the KIN-2787 data release, the company anticipates disclosing its next program from the Kinnate Discovery Engine, which is expected to enter the clinic in 2023.
Announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for KIN-2787 for treatment of patients with BRAF Class II or III alteration-positive and/or NRAS mutation-positive stage IIb to IV malignant melanoma that is metastatic or unresectable. (View Release)
Corporate Highlights

Expanded the organization to 86 full-time employees as of September 30, 2022, of which 64 were engaged in research and development activities.
Third Quarter 2022 Financial Results

Cash and Cash Equivalents and Investments Position: As of September 30, 2022, the total of cash and cash equivalents and investments was $262.1 million, excluding cash from its China joint venture, Kinnjiu, and is expected to fund current operations into mid-2024.
Research and Development Expenses: Third quarter research and development expenses for 2022 were $23.5 million, compared to $18.7 million for the same period in 2021.
General and Administrative Expenses: Third quarter general and administrative expenses for 2022 were $7.8 million, compared to $6.1 million for the same period in 2021.
Net Loss: Third quarter net loss for 2022 was $30.7 million, compared to $24.7 million for the same period in 2021.

On November 10, 2022 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported the publication of data in The Lancet Haematology, which summarizes the Phase 1 results of the Phase 1/2 study of olutasidenib, an investigational, oral, small molecule inhibitor of mutant isocitrate dehydrogenase-1 (mIDH1) (Press release, Rigel, NOV 10, 2022, View Source [SID1234623710]). Olutasidenib was assessed as a monotherapy or in combination with azacitidine, in patients with mIDH1 acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The published data suggest that olutasidenib, with or without azacitidine, was well-tolerated and was associated with improvements in clinical efficacy endpoints in patients with mIDH1 AML.

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"These data from the first phase of the Phase 1/2 study suggest that olutasidenib may be both efficacious and well-tolerated, findings that are reinforced by the subsequently reported data from the Phase 2 registrational trial, which generated compelling efficacy and safety data that highlight olutasidenib as a potential treatment option for mIDH1 relapsed/refractory AML," said Wolfgang Dummer, M.D., Ph.D., Rigel’s chief medical officer. "The NDA for olutasidenib, submitted by Forma Therapeutics, is under FDA review and we look forward to a potential approval in early 2023."

The objectives of the first phase of the multi-center, open-label Phase 1/2 study were to assess the safety, pharmacokinetic and pharmacodynamic profile, and clinical activity of olutasidenib, both as monotherapy and in combination with azacitidine, in patients with treatment-naïve or relapsed/refractory (R/R) AML or MDS harboring IDH1 mutations.

Key findings from the study are summarized below:

Among patients receiving combination therapy, treatment-naïve AML patients saw a 77% overall response rate (ORR) and a 54% complete response (CR) plus CR with partial hematological recovery (CR/CRh). These results provide strong rationale for future evaluation of either sequential or triplet therapy in this setting.
In the MDS cohort, 4 of 9 responding patients achieved mutation clearance. CRs were observed with both monotherapy and combination therapy, including an 86% ORR and 57% CR rate in the combination arm. The investigators noted, "To our knowledge, we also report the first available data on patients with myelodysplastic syndrome treated with an IDH1 inhibitor plus azacitidine, where we observed a strong preliminary activity signal."
Olutasidenib was well-tolerated in patients with AML and MDS, either as monotherapy or in combination with azacitidine. No dose limiting toxicities occurred in the dose escalation cohorts. Overall, adverse events were similar and manageable across the monotherapy and combination arms. Transient QT prolongation was observed in 3 patients (4%).
This study showed that olutasidenib has the potential to provide an additional treatment option for mIDH1 AML.
A link to the online publication at The Lancet Haematology can be found here.

Last week, Rigel announced updated interim data from the Phase 2 pivotal cohort of this trial. This data will be presented in a poster at the 64th ASH (Free ASH Whitepaper) Meeting in New Orleans on December 11, 2022. A link to the press release can be found here.

On August 2, 2022, Rigel and Forma Therapeutics, Inc. announced they entered into an exclusive, worldwide license agreement to develop, manufacture and commercialize olutasidenib for the treatment of relapsed/refractory AML (R/R AML) and other malignancies. Forma’s New Drug Application (NDA) for olutasidenib is currently under review by the U.S. Food and Drug Administration (FDA) and the Prescription Drug User Fee Act (PDUFA) target action date is February 15, 2023.

About Olutasidenib and AML
Olutasidenib is an oral, small molecule investigational agent designed to selectively bind to and inhibit mutated IDH1 enzymes. This targeted treatment has the potential to provide therapeutic benefit by reducing 2-HG levels and restoring normal cellular differentiation. IDH1 is a natural enzyme that is part of the normal metabolism of all cells. When mutated, IDH1 activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 6 to 9 percent of patients with AML1.

AML is a rapidly progressing cancer of the bone marrow and blood2. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that in the United States, there will be about 20,050 new cases of AML in 2022, mostly in adults.3 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.