On October 31, 2023 Nouscom, a clinical-stage immuno-oncology company developing off-the-shelf and personalized viral vector based cancer vaccines, reported that promising interim data from a Phase 1b trial evaluating NOUS-209 in Lynch Syndrome (LS) carriers was published in a Late-breaking Abstract and will be presented in an oral abstract presentation on 4th November 2023 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in San Diego, USA (Press release, NousCom, OCT 31, 2023, View Source;utm_medium=rss&utm_campaign=nouscoms-off-the-shelf-cancer-vaccine-nous-209-shows-potential-to-intercept-cancer-in-subjects-with-lynch-syndrome [SID1234636547]).

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NOUS-209 is an off-the-shelf cancer vaccine encoding 209 neoantigens that are shared across both sporadic and hereditary Microsatellite Instable (MSI) tumors. Patients with LS carry a high-risk hereditary predisposition to developing MSI tumors, and once diagnosed, carriers are encouraged to have routine colonoscopy and endoscopy screenings with the potential of surgery currently as the primary treatment option.

In this single-arm, open-label preventive Phase 1b study (NCT05078866), NOUS-209 monotherapy was found to be safe, well tolerated and able to generate potent and broad immunogenic T cell responses in the first 10 LS participants recruited. The study was led by researchers at The University of Texas MD Anderson Cancer Center, in collaboration with the Cancer Prevention Clinical Trials Network and sponsored by the National Cancer Institute.

NOUS-209 is also being evaluated in ongoing and actively enrolling randomized Phase 2 clinical trials (NCT04041310) in combination with checkpoint inhibitors in patients with metastatic MSI tumors.

As of date of interim data cutoff, no serious adverse events were observed following intramuscular administration of NOUS-209. Vaccination with NOUS-209 is considered safe and well tolerated, with rapid resolution of local and systemic reactogenicity. NOUS-209 immunogenicity has been tested and demonstrated through ex-vivo interferon-gamma ELISpot assay in 100% of tested LS subjects (n=10 out 10 subjects), with no immune responses detectable prior to NOUS-209 administration. Vaccine-induced responses were broad and recognized multiple different neoantigens, potently inducing both CD4 and CD8 T cell responses. The Phase 1b study is enrolling up to 45 LS subjects across multiple US sites and is expected to be fully enrolled by early 2024.

Dr Eduardo Vilar-Sanchez, M.D., Ph.D., Professor of Clinical Cancer Prevention, at MD Anderson and Principal Investigator on the study, said: "The work of the Cancer Prevention Clinical Trials Network is to support early trials that may give LS patients a new way to intercept cancer and possibly lower their cancer risk over time. The presented data suggest that a novel vaccine such as NOUS-209 could provide a compelling approach for cancer interception in LS carriers."

Dr Elisa Scarselli, Chief Scientific Officer of Nouscom added: "These first data demonstrate that NOUS-209 monotherapy can potently and broadly stimulate the immune system in LS subjects, so as to be ready to intercept the development of MSI tumors at an early stage. We are deeply indebted to all our collaborators at the NCI and LS trial volunteers, who collectively are highly motivated in our goal to intercept cancer."

Dr Richard Davis, Chief Operating Officer of Nouscom, commented: "These data are a testament to the power of a true collaboration between industry and academia in our shared ambition to intercept cancer before it can take hold for the huge numbers of LS carriers. We look forward to reporting the full Phase 1b results and outlining the next steps in initiating randomized Phase 2 trials next year."

Oral Abstract Presentation Details:

Title: NOUS-209 genetic vaccine encoding shared cancer neoantigens is safe and elicits robust immune response in healthy Lynch syndrome carriers: interim results from Phase 1 cancer interception trial
Abstract number: 1526
Date & Time: Saturday 4th November 2023; 11:25 AM – 11:55 AM EDT
Session: Late-Breaking Abstract Session
Presenter: Anna Morena D’Alise, VP of Immunology Nouscom
Ends

About Lynch Syndrome

Lynch Syndrome (LS) affects approximately 1 in 300 people and is one of the most common hereditary cancer syndromes, with carriers at high risk of developing microsatellite instability (MSI) cancers, including colorectal or endometrial cancers. LS is caused by mutations in one of the four DNA mismatch repair (MMR) genes that as a result lead to tumors accumulating large number of neoantigens. Vaccine-based strategies to target neoantigens, such as NOUS-209, are being explored in their ability to stimulate the immune system to recognize and intercept tumors at their early stages of development.

On October 31, 2023 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical-stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported validation for the European patent 2019213664 titled "METHODS FOR PRODUCING (6S,15S)-3,8,13,18-TETRAAZAICOSANE-6,15-DIOL" in the United Kingdom, Italy, Germany, France, and Spain (Press release, Panbela Therapeutics, OCT 31, 2023, View Source;utm_medium=rss&utm_campaign=panbela-announces-validation-of-european-patent-for-claims-of-a-novel-process-for-the-production-of-sbp-101 [SID1234636548]). This patent, developed in collaboration with Syngene International Ltd., an integrated research, development, and manufacturing services company, claims a novel process with a reduced number of synthetic steps from seventeen to six to produce SBP-101, a lead investigational product. The patent is valid until 2039.

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Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela Therapeutics, commented, "We’re excited to have this European patent now validated in individual countries." First issued in the United States in 2021 and now in several other territories, this patent covers a shorter synthesis of SBP-101, which provides many benefits including a scalable, efficient and cost-effective manufacturing process to enable future commercialization. Jonathan Hunt, Managing Director and Chief Executive Officer, Syngene International Ltd., said, "Our partnership with Panbela exemplifies Syngene’s commitment to fostering innovation and collaboration in the pharmaceutical industry. Reducing the manufacturing steps of SBP-101 from seventeen to just six not only accelerates the delivery of this promising drug to patients but also underscores Syngene’s dedication to improving efficiency. This patent validation in certain European countries is a testament to our combined expertise and commitment to improving patient outcomes.

We are proud to stand alongside Panbela as we continue to push the boundaries of pharmaceutical innovation." Dr. Simpson added, "We are pleased with the continued growth of our patent portfolio with the validation in several European countries. With a pharmaceutical starting material that is more widely available and a process that is effective and scalable, this ensures a stable drug supply for current clinical trials and future endeavors."

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, ovarian cancer and diabetes. The combined development programs have a steady cadence of catalysts with programs ranging from pre-clinical to registration studies.

SBP-101 Ivospemin

Ivospemin 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. It has shown signals of tumor growth inhibition in clinical studies of metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months and an objective response rate (ORR) of 48%, both exceeding what is typical for 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, ivospemin 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 previous Panbela-sponsored clinical trials provide support for continued evaluation of ivospemin in the ASPIRE trial. For more information, please visit View Source

Flynpovi

Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increase polyamine export and catabolism. In a Phase 3 clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase 3 trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), Flynpovi showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI 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 Eflornithine

CPP-1X (eflornithine) is being developed as a single agent tablet or high dose power sachet for several indications including prevention of gastric cancer and recent onset Type 1 diabetes. Preclinical studies as well as Phase 1 or Phase 2 investigator-initiated trials suggest that CPP-1X treatment may be well-tolerated and has potential activity.

On October 31, 2023 Neurocrine Biosciences, Inc. (Nasdaq: NBIX) reported its financial results for the third quarter ended September 30, 2023, raised 2023 net sales guidance for INGREZZA, and announced an Analyst Day to be held in New York City on December 5th (Press release, Neurocrine Biosciences, OCT 31, 2023, View Source [SID1234636546]).

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"With INGREZZA sales continuing to grow, an expanded indication to treat chorea associated with Huntington’s disease, and positive Phase 3 results in congenital adrenal hyperplasia, Neurocrine remains well positioned to build a leading neuroscience-focused company," said Kevin Gorman, Ph.D., Chief Executive Officer of Neurocrine Biosciences. "We look forward to sharing more insight into our R&D portfolio and strategy at our December Analyst Day."

Three Months Ended

September 30,

Nine Months Ended

September 30,

(unaudited, in millions, except per share data)

2023

2022

2023

2022

Revenues:

Net Product Sales

$ 491.8

$ 379.3

$ 1,353.4

$ 1,036.3

Collaboration Revenue

7.0

8.6

18.5

40.4

Total Revenues

$ 498.8

$ 387.9

$ 1,371.9

$ 1,076.7

GAAP Research and Development (R&D)

$ 142.2

$ 107.7

$ 427.5

$ 345.8

Non-GAAP R&D

$ 125.0

$ 92.8

$ 372.7

$ 302.2

GAAP Selling, General and Administrative (SG&A)

$ 204.2

$ 186.3

$ 668.7

$ 569.8

Non-GAAP SG&A

$ 169.7

$ 158.1

$ 563.4

$ 483.8

GAAP Net Income

$ 83.1

$ 68.5

$ 102.0

$ 65.5

GAAP Earnings Per Share – Diluted

$ 0.82

$ 0.69

$ 1.01

$ 0.67

Non-GAAP Net Income

$ 156.1

$ 106.7

$ 232.3

$ 218.5

Non-GAAP Earnings Per Share – Diluted

$ 1.54

$ 1.08

$ 2.31

$ 2.22

(unaudited, in millions)

September 30,

2023

December 31,

2022

Total Cash, Cash Equivalents and Marketable Securities

$ 1,549.8

$ 1,288.7

Third Quarter INGREZZA Net Product Sales Highlights:

INGREZZA third quarter 2023 net product sales were $486 million and grew 29% vs. the third quarter 2022 driven by prescription demand
Continued high level of new patient scripts generated in the third quarter of 2023
Third Quarter Financial Highlights:

Third quarter 2023 GAAP net income and earnings per share of $83 million and $0.82, respectively, compared with $69 million and $0.69, respectively, for third quarter 2022
Third quarter 2023 non-GAAP net income and earnings per share of $156 million and $1.54, respectively, compared with $107 million and $1.08, respectively, for third quarter 2022
Differences in third quarter 2023 GAAP and non-GAAP operating expenses compared with third quarter 2022 driven by:
Increased R&D expense in support of an expanded and advancing clinical portfolio including preclinical investments in VMAT2, crinecerfont, and our muscarinic compounds
Increased SG&A expense primarily due to ongoing commercial initiatives supporting INGREZZA growth including the expanded indication to treat chorea associated with Huntington’s disease
At September 30, 2023, the Company had cash, cash equivalents and marketable securities of approximately $1.5 billion
A reconciliation of GAAP to non-GAAP financial results can be found in Table 3 and Table 4 at the end of this earnings release.

Recent Events:

In August 2023, the FDA approved INGREZZA for the treatment of adults with chorea associated with Huntington’s disease.
In September 2023, the Company announced the FDA accepted its New Drug Application (NDA) for INGREZZA oral granules, a new sprinkle formulation of INGREZZA capsules for oral administration. The agency set a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2024.
In September 2023, the Company announced positive top-line data from the Phase 3 CAHtalyst clinical study of crinecerfont in adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). The study met its primary as well as important key secondary endpoints.
In October 2023, the Company announced positive top-line data from the Phase 3 CAHtalyst clinical study of crinecerfont in pediatrics with CAH due to 21-hydroxylase deficiency (21-OHD). The study met both its primary and key secondary endpoint.
Updated 2023 INGREZZA Sales Guidance and Operating Expense Guidance:

Range

(in millions)

Low

High

INGREZZA Net Product Sales 1

$ 1,820

$ 1,840

GAAP R&D Expense 2

$ 560

$ 570

Non-GAAP R&D Expense 3

$ 490

$ 500

GAAP and Non-GAAP IPR&D 4

$ 144

$ 144

GAAP SG&A Expense 5

$ 870

$ 890

Non-GAAP SG&A Expense 3

$ 740

$ 760

1. INGREZZA sales guidance for fiscal 2023 reflects expected sales of INGREZZA.

2. GAAP R&D guidance includes amounts for milestones that are probable of achievement or have been achieved.

3. Non-GAAP guidance adjusted primarily to exclude estimated non-cash stock-based compensation expense of $70 million in R&D and $125 million in SG&A.

4. IPR&D guidance reflects acquired in-process research and development once significant collaboration and licensing arrangements have been completed. IPR&D guidance includes $143.9 million associated with the new strategic collaboration with Voyager.

5. SG&A guidance range reflects increased spend following INGREZZA expanded indication to treat chorea associated with Huntington’s disease and positive Phase 3 results in CAH.

Conference Call and Webcast Today at 8:00 AM Eastern Time
Neurocrine Biosciences will hold a live conference call and webcast today at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the live conference call by dialing 800-895-3361 (US) or 785-424-1062 (International) using the conference ID: NBIX. The webcast can also be accessed on Neurocrine Biosciences’ website under Investors at www.neurocrine.com. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month.

On October 31, 2023 Myriad Genetics, Inc. (the "Company") reported to have entered into an amendment (the "Amendment") to (i) its original credit agreement (the "Original Credit Agreement") dated as of June 30, 2023, with the lenders from time to time party thereto, certain of the Company’s domestic subsidiaries party thereto (the "Guarantors"), and JP Morgan Chase Bank, N.A., as Administrative Agent (in such capacity, "Administrative Agent") and as Issuing Bank, consisting of a revolving credit facility in an initial maximum principal amount of $90,000,000, with an option to increase the maximum principal amount by up to $25,000,000 and (ii) its original pledge and security agreement (the "Original Security Agreement") dated as of June 30, 2023, with the other grantors party thereto and the Administrative Agent (Filing, 8-K, Myriad Genetics, OCT 31, 2023, View Source [SID1234636541]). Pursuant to the Amendment, the Company exercised the option to increase the maximum principal amount of the available revolving line of credit by $25,000,000, which was effectuated through a new commitment provided by a new lender, Goldman Sachs Bank USA.

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In addition, the Amendment amends the Original Credit Agreement and Original Security Agreement to, among other things, the following:

•allow for the assignment and terminations of certain lease agreements and the sale of certain personal property consisting of office furniture and equipment relating to such assignment;
•extend the time for compliance with certain post-closing obligations of the Original Credit Agreement; and
•revise the language of the Original Security Agreement to better reflect the Company’s existing cash management system.

The foregoing description of the Amendment does not purport to be complete and is qualified in its entirety by reference to the complete text of the Amendment, a copy of which is attached as Exhibit 10.1 to this Current Report on Form 8-K and incorporated herein by reference in its entirety.

On October 31, 2023 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on the company’s Phase 1 clinical trial of XMT-2056 (Press release, Mersana Therapeutics, OCT 31, 2023, View Source [SID1234636539]). XMT-2056 is a systemically administered Immunosynthen STING-agonist ADC that is designed to target a novel human epidermal growth factor receptor 2 (HER2) epitope and locally activate STING signaling in both tumor-resident immune cells and in tumor cells, providing the potential to treat patients with HER2-high or -low tumors as monotherapy and in combination with standard-of-care agents.

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"An in-depth analysis of cytokine, pharmacokinetic and other clinical data from patients enrolled in our Phase 1 trial indicated that XMT-2056 is a highly potent innate immune agonist," said Martin Huber, M.D., President and Chief Executive Officer of Mersana Therapeutics. "Based on these data and with patient safety at the forefront of our efforts, we have lowered the starting dose in our Phase 1 dose escalation design. We are pleased to have aligned with FDA on the path forward and are excited to have the opportunity to continue to investigate the potential of XMT-2056 and our Immunosynthen ADC platform in the clinic."

The multicenter Phase 1 open-label trial is investigating XMT-2056 in previously treated patients with advanced/recurrent solid tumors expressing HER2, including breast, gastric, colorectal and non-small-cell lung cancers. The dose escalation and dose expansion portions of the trial will evaluate and characterize the relationship of safety, tolerability and exposure of XMT-2056 and this candidate’s preliminary anti-tumor activity, as measured by overall response rate, duration of response and disease control rate.

The FDA has granted orphan drug designation to XMT-2056 for the treatment of gastric cancer. In August 2022, Mersana entered into a global collaboration providing GSK plc with an exclusive option to co-develop and commercialize XMT-2056. GSK has not exercised this option to date.