On March 21, 2024 Oxcia reported that it has obtained approval from the South African Health Products Regulatory Authority, (SAHPRA) for the start of the phase 1 / 2 study of OXC-101 in solid cancers, more specifically gynecological cancers, prostate cancer and head and neck cancer (Press release, Oxcia, MAR 21, 2024, View Source;utm_medium=rss&utm_campaign=key-milestone-for-oxc-101-study-approval-in-south-africa [SID1234641346]). The study will take place at two clinical sites in South Africa. Oxcia is now applying for ethical approval and sending in a protocol amendment. The study is estimated to start early to mid-summer.

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"I am thrilled for this opportunity to build further clinical experience with OXC-101 and demonstrate safety and efficacy in less heavily pretreated patients than those treated so far" says Ulrika Warpman Berglund, CEO at Oxcia.

The clinical phase 1 / 2 study with OXC-101 in advanced solid cancers has already been extended in Sweden. Recruitment of patients with prostate and gynecological cancer is ongoing. The goal is to gather more clinical data with OXC-101 and align with regulatory agencies on the optimal effective dose and move into phase 2 development once capital has been secured.

For further information, please contact:

Ulrika Warpman Berglund, CEO

Phone: +46 (0) 73 270 96 05

Email: [email protected]

Briefly about OXC-101

OXC-101 is a "mitotic MTH1 inhibitor" and belongs to a completely new class of cancer drugs. It has potential for broad anticancer effect and suitability for large patient populations. It is given as a tablet. OXC-101 has demonstrated clinical benefits which supports further development in the phase 1 MASTIFF study.

OXC-101 makes intelligent use of the cancer cell’s inherent high levels of oxidative DNA damage and oxidative stress. OXC-101 stops cancer cell division by preventing microtubules from functioning. This generates additional oxidative stress (ie, ROS) and increased levels of oxidatively damaged DNA building blocks. By inhibiting MTH1, more damaged DNA building blocks remain and build into the DNA, causing even more DNA damage. The cancer cell can no longer handle the high levels of oxidative stress and DNA damage, resulting in the death of the cancer cell.

On March 21, 2024 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported financial results for the fourth quarter and year ended December 31, 2023 (Press release, Nkarta, MAR 21, 2024, View Source [SID1234641345]).

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"Patients with severe autoimmune diseases deserve novel, effective treatments," noted Paul J. Hastings, President and CEO of Nkarta. "Recent academic studies have shown that CD19-directed cell therapy has the promise to be truly transformative, and we believe that NKX019 may replicate these early results with superior safety and accessibility. Our approach leverages the potential advantages of NK cells, including fludarabine-free lymphodepletion, deep and rapid B-cell depletion, and the added utility of on-demand dosing. Work with investigators, sites and patients is advancing rapidly, and we remain on track to initiate dosing in our clinical trial of NKX019 in refractory lupus nephritis in the first half of 2024."

Hastings continued, "The potential of NKX019 to transform the treatment landscape in autoimmune disease demands our focus. To support our early-mover advantage and advance this program, Nkarta has deprioritized the development of NKX101. This follows a planned interim evaluation of Phase 1 data from NKX101 that included 14 new patients with AML. While the safety profile remained encouraging, the response rate was meaningfully lower than that from the first 6 previously reported patients. We see promise in NKX101, but before pursuing further development or significant investment, we will evaluate options for optimizing future study design, dosing schedule and manufacturing. We are grateful for the support of the NKX101 investigators as well as their patients for their commitment and trust."

NKX019 in autoimmune disease

In October 2023, Nkarta announced the expansion of its pipeline to include autoimmune disease following the clearance by FDA of the IND application for NKX019 in lupus nephritis (LN).
The multi-center, open label, dose escalation clinical trial will assess the safety and clinical activity of NKX019 in up to 12 patients with refractory LN. Patients will receive a three-dose cycle of NKX019 at 1 billion or 1.5 billion cells per dose following lymphodepletion (LD) with single agent cyclophosphamide (cy), an agent with an established safety profile in systemic lupus erythematosus (SLE) and LN.
Nkarta plans to dose the first patient in the LN study in the first half of 2024.
NKX019 is highly active against B cells from patients with multiple autoimmune diseases, and Nkarta is evaluating additional indications for potential clinical investigation with NKX019.
NKX019 in non-Hodgkin lymphoma (NHL)

In October 2023, Nkarta announced a new cohort in its Phase 1 study of NKX019 in relapsed/refractory (r/r) NHL. The cohort (n=6) introduces a compressed dosing schedule, where patients receive NKX019 doses on Days 0, 3 and 7 following LD with fludarabine (flu) and cy. This regimen is designed to intensify exposure of NKX019 by dosing closer to LD. In addition, patients with ongoing cytopenias have the potential to receive NKX019 following LD with cy alone.
Nkarta expects to announce preliminary data from the NKX019 compressed dosing cohort in mid-2024.
Nkarta is no longer enrolling patients in the cohorts in which NKX019 was being administered on Days 0, 7 and 14 following LD. Future development of NKX019 in the NHL indication will be contingent on favorable outcomes from the compressed dosing cohort.
In June 2023, Nkarta presented preliminary clinical data based on a November 2022 data cut-off from its Phase 1 clinical trial of NKX019 in patients with r/r NHL at the annual meeting of the European Hematology Association (EHA) (Free EHA Whitepaper) and the International Conference on Malignant Lymphoma. 7 of 10 patients achieved complete response (70% CR rate) following treatment with NKX019 monotherapy at highest dose levels.
In January 2024, Nkarta reported that 4 of 4 patients with r/r NHL that relapsed after achieving CR following treatment with NKX019 were again able to achieve CR after re-treatment with NKX019. These outcomes suggest that relapse, when it occurs, may be attributable to mechanisms of NKX019 exposure and not resistance to NKX019.
NKX101 in acute myeloid leukemia (AML)

Nkarta announced today that it has closed patient enrollment in its clinical trial of NKX101 and deprioritized the program as part of a pipeline realignment that directs primary resources to its lead pipeline program, NKX019, for the treatment of autoimmune disease. This follows a recent review of preliminary safety and response data from patients with r/r AML that received NKX101 after LD comprising fludarabine and cytarabine (flu/Ara-C). The aggregate CR/CRi rate (5 of 20 patients) was lower than what had been observed in the first 6 patients in the cohort. The safety profile of NKX101 was consistent with previously reported data.
This announcement reflects the NKX101 clinical update that Nkarta had planned to report in the first half of 2024. Nkarta plans to present these data at a future medical conference.
In June 2023, Nkarta reported updated clinical data from its Phase 1 clinical trial evaluating NKX101 in patients with relapsed or refractory (r/r) AML. In the first 6 patients that received NKX101 after flu/Ara-C LD, 4 of 6 achieved CR/CRi as of the data cut-off on June 10, 2023. In a follow-up report on these 6 patients presented at the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), of those patients who achieved CR/CRi, 3 of 4 remained in CR/CRi at 4 months as of the data cut off on October 31, 2023.
Fourth Quarter and Full Year 2023 Financial Highlights

As of December 31, 2023, Nkarta had cash, cash equivalents, and investments of $250.9 million, including restricted cash of $2.7 million.
Research and development (R&D) expenses were $96.8 million for the full year 2023 and $23.3 million for the fourth quarter of 2023. Non-cash stock-based compensation expense included in R&D expense was $8.0 million for the full year 2023 and $1.7 million for the fourth quarter of 2023.
General and administrative (G&A) expenses were $34.9 million for the full year 2023 and $7.9 million for the fourth quarter of 2023. Non-cash stock-based compensation expense included in G&A expense was $9.2 million for the full year 2023 and $1.8 million for the fourth quarter of 2023.
Net loss was $117.5 million, or $2.40 per basic and diluted share, for the full year 2023. This net loss includes non-cash charges of $26.5 million that consisted primarily of share-based compensation, depreciation, and an impairment charge against right-of-use assets that Nkarta plans to sublease. Net loss was $27.8 million, or $0.57 per basic and diluted share, for the fourth quarter of 2023.
Financial Guidance

Nkarta expects its current cash and cash equivalents will be sufficient to fund its current operating plan into 2026.
About NKX019
NKX019 is an allogeneic, cryopreserved, off-the-shelf immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal B cells as well as those implicated in autoimmune disease and B cell-derived malignancies.

About NKX101
NKX101 is an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy donors. It is engineered with a chimeric antigen receptor (CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key activating receptor found on naturally occurring NK cells, induces a cell-killing immune response through the detection of stress ligands that are widely expressed on cancer cells. NKX101 is also engineered with a membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support.

On March 21, 2024 NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class and best-in-class therapies to treat cancer reported a business update and provided full year 2023 financial results (Press release, NextCure, MAR 21, 2024, View Source [SID1234641344]).

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"Clinical data generated in 2023 enabled us to objectively assess each program and set our priorities for 2024. Based on that assessment, we will prioritize NC410 combo and LNCB74 in 2024, while seeking to partner our other portfolio assets," said Michael Richman, NextCure’s president and chief executive officer. "These strategic decisions have led to restructuring our workforce reflecting our reduced need for internal GMP manufacturing operations. We believe we have sufficient inventory to support our currently planned clinical trials. I wish to thank those employees who are impacted today for their contributions and dedication to our mission."

Mr. Richman continued, "We are excited to focus on NC410 combo, which is demonstrating clinical responses in ovarian and colorectal cancers. We are advancing LNCB74 in collaboration with LegoChem Biosciences, a differentiated ADC directed to B7-H4, a clinically validated cancer target. Given our current cash position and revised runway to the second half of 2026, we believe we can advance our two programs through important near-term clinical milestones."

Business Highlights and Near-Term Milestones

Prioritized Programs

NC410 (LAIR-2 fusion)

● The multi-center, multi-arm, first-in-human Phase 1b combination trial is evaluating the efficacy of NC410 in combination with pembrolizumab. Indications include: (i) ICI Naïve and refractory ovarian cancer and (ii) microsatellite stable (MSS) / microsatellite instability low (MSI-L) immune checkpoint inhibitor (ICI) Naïve and refractory colorectal cancer (CRC). The combination has been shown to be
well tolerated up to 200 mg of NC410 with Grade 3 or higher Treatment Related Adverse Events of 3.7%.
NC410 for Ovarian Cancer

● Evidence of early clinical activity and biomarker observations support the proposed mechanism of action for NC410 in relapsed/refractory ICI Naïve ovarian cancer, with/without active liver metastasis for subjects in the 100 mg and 200 mg cohorts. As of February 23, 2024, the findings of the initial 7 evaluable patients based on RECIST 1.1 are summarized in the table below:
Relapsed/Refractory ICI Naïve Ovarian, 100 mg and 200 mg cohorts

Evaluable Patients as of February 23, 2024

n=7

Overall Response rate (ORR)

42.8%, n=3

Disease Control Rate (DCR)

42.8%, n=3

Evidence supporting mechanism of action

Observed in biomarker data

● Additional observations from the initial 7-patient data set as of February 23, 2024, include:
o 3 partial responses (PR) were observed at the initial 9-week scan.
o 1 confirmed PR observed in the 200 mg cohort continues on study beyond 6 months.
o The 2 PRs at the 100 mg cohort are pending confirmatory scans at week 18.
● Biomarker data on blood samples drawn from patients in both the prior NC410 monotherapy trial and, the current NC410 combo trial support our hypothesis regarding the mechanism of action (MOA) and activity in PR patients as follows:
o Decrease in peripheral Granzyme B-expressing CD8+ T cells, which supports our mechanism of action (MOA) that NC410 remodels the extracellular matrix (ECM) allowing activated immune cells to infiltrate into the tumor microenvironment (TME). Generation of collagen-derived product 4GZ fragments is mediated by Granzyme B-expressing T cells and provides direct evidence of ECM remodeling and correlates with responses.
o Decrease in peripheral myeloid-derived suppressor cells reduces suppressive effects and enhances activation of immune cells and anti-tumor activity.
o Decrease in peripheral CCR7+ DC+ T cells which is consistent with chemokine guided migration of immune cells to the TME.
● Taken together, the data demonstrate that NC410 mediates activation of immune cells and migration into the TME through remodeling of the ECM. We believe NC410 combo results in anti-tumor activity and clinical responses in patients that have been shown to respond poorly to or are resistant to checkpoint inhibitors.
● In March 2024, we commenced enrolling an additional 18 patients among the 100 mg and 200 mg cohorts. We plan to present the data from the ovarian cancer patients in the second half of 2024.
NC410 Colorectal Cancer (CRC)

● Preliminary evidence of clinical activity in the 100 mg cohort of patients with MSS/ MSI-L ICI naïve CRC without active liver metastasis (LM-). The findings as of February 23, 2024, of the initial 19 evaluable patients are summarized based on RECIST 1.1 guideline in the table below:
MSS/MSI-L ICI Naïve CRC, LM-, 100 mg cohort

Evaluable Patients as of February 23, 2024

n=19

Overall Response rate (ORR)

10.5%, n=2

Disease Control Rate (DCR)

47.3%, n=9

Median Progression Free Survival (mPFS)

8.1 months

● Additional observations from the 19-patient data set as of February 23, 2024:
o Both responses were observed at the initial 9-week scan in the 100 mg cohort.
o Subjects enrolled had a median of 5 lines of prior treatment.
o The 2 responders remain as PRs, and continue on study for over 10 months and 5 months, respectively.
● Completed enrollment in January 2024 of an additional 20 patients in the 100 mg cohort. We plan to present the data of the CRC patients at a scientific conference within the second quarter of 2024.
LNCB74 (B7-H4 ADC)

● Selected our first antibody drug conjugate (ADC) candidate of a potential of three from our collaboration with LegoChem Biosciences, Inc. (LegoChem). Under the terms of the Agreement, both parties equally share the costs of developing the molecules and profits on commercialized products.
● Commenced development of LNCB74 utilizing a NextCure B7-H4 antibody and LegoChem’s ConjuAllTM ADC technology.
● Differentiated approach leveraging:
o B7-H4 specific antibody with an Fc modification that protects immune cells to improve safety
o Use of a glucuronidase cleavable linker that offers cancer-selective payload release to minimize toxicity in non-tumor cells, and
o Use of a monomethyl auristatin E (MMAE) payload with a drug-to-antibody ratio (DAR) of 4, that has the advantage of bystander killing of surrounding tumor cells.
● Pre-clinical experiments in vitro and in vivo demonstrating potent tumor killing and pilot toxicology studies have been completed.
● Pre-filing feedback from the FDA supports moving forward to planned submission of an IND application by this year-end.
● Ongoing activities associated with GLP toxicity studies, GMP manufacturing, and clinical development planning are in progress.

Assets We Intend to Partner

● NC525 is a novel LAIR-1 antibody that selectively targets Acute Myeloid Leukemia (AML) blast cells and leukemic stem cells, and currently is in a Phase 1a monotherapy dose escalation and safety study evaluating NC525 in AML patients. The trial is now in the fifth dose escalation cohort, and we plan to complete the dose-finding portion of the study to arrive at a predicted biologically active dose and further assess development plans by the fourth quarter of 2024.

● NC605 is an antibody that targets Siglec-15 and has the potential as a treatment for bone disease. Preclinical data show that NC605 treatment reduced bone loss and enhanced bone quality in mice with osteogenesis imperfecta (OI). OI is a rare disorder that results in high bone turnover, abnormal bone formation, bone fragility, and recurrent fractures. NC605 could also have applications in chronic bone diseases such as osteoarthritis and non-union fractures. We are currently conducting toxicology studies in preparation for partnering.
● NC181 is a humanized antibody targeting ApoE4 for the treatment of Alzheimer’s disease (AD). In preclinical AD animal models, NC181 has demonstrated amyloid clearance, prevention of amyloid deposition, plaque clearance and neuroinflammation reduction. Preclinical studies have demonstrated that it reduces microhemorrhages, improves cerebral vascular function and lowers risk of Amyloid Related Imaging Abnormalities (ARIA).

Restructuring of Operations

● Implemented a restructuring plan to reduce operating costs and better align our workforce with the needs of our business. Under the plan, we paused our internal manufacturing operations and reduced our workforce by approximately 37%. We estimate that we will incur one-time restructuring charges of approximately $0.8 million including employee severance, benefits and related termination costs, the majority of which we expect to pay in the second quarter of 2024.

Financial Guidance

● NextCure expects its existing cash, cash equivalents and marketable securities will enable it to fund operating expenses and capital expenditures into the second half of 2026.

Financial Results for Full Year Ended December 31, 2023

● Cash, cash equivalents, and marketable securities as of December 31, 2023, were $108.3 million as compared to $159.9 million as of December 31, 2022. The decrease of $51.6 million was primarily due to cash used to fund operations, and cash used to purchase fixed assets.
● Research and development expenses were $47.9 million for the year ended December 31, 2023, as compared to $54.2 million for the year ended December 31, 2022. The decrease of $6.3 million was primarily due to lower costs related to our clinical programs.
● General and administrative expenses were $19.7 million for the year ended December 31, 2023, as compared to $21.7 million for the year ended December 31, 2022. The decrease of $2.0 million was primarily related to lower personnel-related costs, including $1.2 million of stock compensation, and lower insurance and professional costs.
● Net loss was $62.7 million for the year ended December 31, 2023, as compared with a net loss of $74.7 million for the year ended December 31, 2022. Lower research and development expenses, lower general and administrative expenses and higher other income contributed to the lower net loss.

On March 21, 2024 Milestone Pharmaceuticals Inc. (Nasdaq: MIST) reported financial results for the fourth quarter and year ended December 31, 2023 and provided a regulatory and corporate update (Press release, Milestone Pharmaceuticals, MAR 21, 2024, View Source [SID1234641343]).

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"We look forward to resubmitting our NDA imminently. With the completion of our recent financing and potential future synthetic royalty payment, we believe we are well positioned to advance etripamil through potential approval and launch in PSVT," said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. "We’re excited to continue this positive momentum as we execute on our programs and advance etripamil."

Corporate Updates

• In March 2024, completed a public offering of common shares and pre-funded warrants, raising net proceeds of approximately $32.4 million. Milestone intends to use the proceeds from the Offering to continue the development of etripamil in its lead indication of paroxysmal supraventricular tachycardia (PSVT) and its subsequent indication of atrial fibrillation with a rapid ventricular rate (AFib-RVR), as well as for working capital and other general corporate purposes.

Recent Program Updates

Etripamil for Patients with PSVT

•
Announced Plans to Resubmit New Drug Application (NDA) for Etripamil for PSVT in early 2Q 2024. Milestone held a Type A meeting with the FDA in February 2024 regarding steps required to resolve the items raised in the Refusal to File (RTF) letter received in December 2023. The Company is working to restructure the data sets that capture timing of reported adverse events (AEs) in the clinical etripamil studies and is reformatting certain data files to facilitate FDA’s analyses. The Company expects a standard NDA review period following resubmission of the NDA.

Etripamil for Patients with AFib-RVR

• Phase 3 guidance received from FDA in 1Q2024 meeting. FDA reiterated prior guidance regarding the availability of a single-study supplemental New Drug Application (sNDA) pathway contingent on obtaining approval for the NDA in PSVT. FDA further concurred with respect to key study elements including powering, inclusion criteria, patient population, and statistical analyses, and offered clarification with respect to the endpoints to guide the design of the Phase 3 study. We anticipate progressing to an End of Phase 2 meeting to finalize the registrational study protocol in mid-2024.

• Positive Results from ReVeRA Phase 2 Study of Etripamil in AFib-RVR Presented as Featured Science at the American Heart Association (AHA) Scientific Sessions 2023 and Simultaneously Published in Circulation: Arrhythmia and Electrophysiology. In November 2023, Milestone announced positive data from the ReVeRA Phase 2 study that show that patients with AFib-RVR receiving etripamil demonstrated rapid and statistically superior ventricular rate reduction and improved symptom-relief when compared to placebo. Safety and tolerability reported in the 56-patient safety population who received etripamil was generally consistent with that observed in the Company’s extensive safety database from the PSVT program. The results were presented as a Featured Science presentation at the American Heart Association (AHA) Scientific Sessions 2023 and simultaneously published in Circulation: Arrhythmia and Electrophysiology, which can be found here.

Fourth Quarter and Full Year 2023 Financial Results

• As of December 31, 2023, Milestone had cash, cash equivalents, and short-term investments of $66.0 million, compared to $64.6 million as of December 31, 2022.

• There was no revenue recorded for the fourth quarter of 2023, compared with $3.5 million the fourth quarter of 2022. Revenue for the full year ended December 31, 2023 was $1.0 million compared to $5.0 million in the year ended December 31, 2022. Revenue in 2023 was related to a milestone payment received from Ji Xing Pharmaceuticals, under the Company’s License and Collaboration Agreement. Revenue in 2022 was related to two milestone payments received under the agreement with Ji Xing Pharmaceuticals.

• Research and development expense for the fourth quarter of 2023 was $5.5 million, compared with $10.6 million for the prior year period. For the full year ended December 31, 2023, research and development expense was $31.1 million, compared with $39.8 million for the prior year. The decrease year over year was primarily due to lower clinical expenses as a result of the completion of Phase 3 studies, partially offset by an increase in drug manufacturing consulting costs, drug manufacturing personnel costs and regulatory consulting costs.

• General and administrative expense for the fourth quarter of 2023 was $3.4 million, compared with $4.1 million for the prior year period. For the full year ended December 31, 2023, general and administrative expense was $15.9 million, compared with $15.7 million for the prior year.

• Commercial expense for the fourth quarter of 2023 was $5.0 million, compared with $2.6 million for the prior year period. For the full year ended December 31, 2023, commercial expense was $15.1 million, compared with $9.1 million for the prior year. The increase in commercial expense year over year was a result of additional personnel and professional costs required to expand capabilities and operations in anticipation of potential commercialization.

• For the fourth quarter of 2023, net loss was $13.6 million, compared to $13.2 million for the prior year period. For the full year ended December 31, 2023, Milestone’s net loss was $59.7 million, compared to $58.4 million for the prior year.

For further details on the Company’s financials, refer to Form 10-K for the year ended December 31, 2023, filed with the SEC.

About Paroxysmal Supraventricular Tachycardia

An estimated two million people in the United States are currently diagnosed with PSVT which is a type of arrhythmia or abnormal heart rhythm. PSVT is characterized by episodes of sudden onset rapid heartbeats often exceeding 150 to 200 beats per minute. The heart rate spike is unpredictable and may last several hours. The rapid heart rate often causes disabling severe palpitations, shortness of breath, chest discomfort, dizziness or lightheadedness, and distress, forcing patients to limit their daily activities. The uncertainty of when an episode of PSVT will strike or how long it will persist can provoke anxiety in patients and negatively impact their day-to-day life between episodes. The impact and morbidity from an attack can be especially detrimental in patients with underlying cardiovascular or medical conditions, such as heart failure, obstructive coronary disease, or dehydration. Many health care providers are dissatisfied with the lack of effective treatment options with patients often requiring prolonged, burdensome, and costly trips to the emergency department or even invasive cardiac ablation procedures.

About Atrial Fibrillation with Rapid Ventricular Rate

An estimated five million Americans suffer from AFib, a common arrhythmia marked by an irregular, disruptive and often rapid heartbeat. The incidence of AFib is expected to grow to approximately 10 million by 2025 and up to about 12 million by 2030. A subset of patients with AFib experience episodes of abnormally high heart rate most often accompanied by palpitations, shortness of breath, dizziness, and weakness. While these episodes, known as AFib-RVR, may be treated by oral calcium channel blockers and/or beta blockers, patients frequently seek acute care in the emergency department to address symptoms. In 2016, nearly 800,000 patients were admitted to the emergency department due to AFib symptoms where treatment includes medically supervised intravenous administration of calcium channel blockers or beta blockers, or electrical cardioversion. With little available data for AFib-RVR, Milestone’s initial market research indicates that 30 to 40% of patients with AFib experience one or more symptomatic episodes of RVR per year that require treatment, suggesting a target addressable market of approximately three to four million patients in 2030 for etripamil in patients with AFib-RVR.

About Etripamil

Etripamil is Milestone’s lead investigational product. It is a novel calcium channel blocker nasal spray under clinical development for frequent and often highly symptomatic episodes of PSVT and AFib-RVR. It is designed as a self-administered rapid response therapy for patients thereby bypassing the need for immediate medical oversight. If approved, etripamil is intended to provide health care providers with a new treatment option to enable on-demand care and patient self-management. This portable, self-administered treatment may provide patients with active management and a greater sense of control over their condition. CARDAMYST, the conditionally approved brand name for etripamil nasal spray, is well studied with a robust clinical trial program that includes a completed Phase 3 clinical-stage program for the treatment of PSVT and Phase 2 trial for the treatment of patients with AFib-RVR.

On March 21, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the Phase 3 KEYLYNK-006 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with maintenance LYNPARZA, a PARP inhibitor, did not meet its dual primary endpoints of overall survival (OS) and progression-free survival (PFS) for the first-line treatment of certain patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) (Press release, Merck & Co, MAR 21, 2024, View Source [SID1234641342]).

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In the KEYLYNK-006 trial, KEYTRUDA in combination with chemotherapy followed by KEYTRUDA plus maintenance LYNPARZA did not meet the study’s pre-specified statistical criteria for OS or PFS compared to KEYTRUDA in combination with chemotherapy (pemetrexed plus carboplatin or cisplatin) followed by KEYTRUDA plus maintenance chemotherapy (pemetrexed). The safety profiles of KEYTRUDA and LYNPARZA in this trial were consistent with those observed in previously reported studies for the individual therapies. A full evaluation of the data from this study is ongoing. Merck will work with investigators to share the results with the scientific community.

"As lung cancer continues to be the leading cause of cancer death worldwide, we are committed to exploring KEYTRUDA-based combinations and novel candidates that may further help improve patient outcomes," said Dr. Gregory Lubiniecki, vice president, global clinical development, Merck Research Laboratories. "These results are an important reminder of how challenging it may be to treat these patients with metastatic nonsquamous non-small cell lung cancer. We sincerely thank the patients and investigators for their important contributions to this study."

About KEYLYNK-006

KEYLYNK-006 is a randomized, open-label, two-phase Phase 3 trial (ClinicalTrials.gov, NCT03976323) evaluating KEYTRUDA in combination with chemotherapy (pemetrexed plus carboplatin or cisplatin) followed by either KEYTRUDA plus maintenance LYNPARZA or KEYTRUDA plus maintenance chemotherapy (pemetrexed) for the first-line treatment of patients with metastatic nonsquamous NSCLC with no epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) or proto-oncogene tyrosine-protein kinase (ROS1) genomic tumor aberrations. The dual primary endpoints are PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR) and OS. The secondary endpoints include safety and health-related quality of life assessments. The trial enrolled an estimated 1,005 patients in the Induction Phase and randomized 672 patients with a complete or partial response or with stable disease. In the Induction Phase, patients received KEYTRUDA (200 mg intravenously [IV]) in combination with pemetrexed plus investigator’s choice of platinum chemotherapy, consisting of either carboplatin Area Under the Curve (AUC) (5 mg/mL/min IV) or cisplatin (75 mg/m2 IV) every three weeks (Q3W) for four cycles. In the Maintenance Phase, patients with a complete or partial response or with stable disease after completing four cycles of induction therapy were randomized to receive either KEYTRUDA (200 mg IV Q3W for up to 31 cycles) plus maintenance LYNPARZA (300 mg orally twice daily) or KEYTRUDA (200 mg IV Q3W for up to 31 cycles) plus maintenance pemetrexed (500 mg/m2 IV Q3W) until progressive disease, physician decision or intolerable toxicity.

About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.