On November 9, 2023 Omeros Corporation (Nasdaq: OMER), a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting immunologic disorders including complement-mediated diseases, cancers, and addictive and compulsive disorders, reported recent highlights and developments as well as financial results for the third quarter ended September 30, 2023, which include (Press release, Omeros, NOV 9, 2023, View Source [SID1234637407]):

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● Net loss was $37.8 million for the quarter ended September 30, 2023, or $0.60 per share, compared to a net loss in the prior year quarter of $17.5 million, or $0.28 per share. The difference in the current year quarter net loss was primarily attributable to an incremental $18.9 million gain in discontinued operations in the prior year quarter due to the remeasurement of the OMIDRIA contract royalty asset. Net loss from continuing operations for the current quarter was $51.7 million compared to a net loss of $54.8 million in the prior year quarter. Cash burn for the quarter was $31.0 million.

● For the nine months ended September 30, 2023, our net loss was $108.8 million, or $1.73 per share, compared to a net loss of $81.3 million, or $1.30 per share, in the prior year period. The primary difference between the periods was the incremental gain from the remeasurement of the contract royalty asset in the prior year. Net loss from continuing operations for the nine months ended September 30, 2023 was $135.6 million compared to a net loss of $136.0 million in the prior year.

● For the third quarter of 2023, we earned OMIDRIA royalties of $10.0 million on Rayner Surgical Inc.’s U.S. net sales of $33.3 million. This compared to earned OMIDRIA royalties of $16.5 million during the third quarter of the prior year on U.S. net sales of $33.0 million. The difference in earned royalties reflects the decrease from 50 percent to 30 percent in the base royalty rate applicable to U.S. net sales of OMIDRIA, which occurred in December 2022 upon achievement of the $200.0 million milestone payment event.

● At September 30, 2023, we had $310.3 million of cash, cash equivalents and short-term investments available for operations and debt servicing. We expect to pay from our existing cash and investments on hand the $95 million principal balance due at maturity of our unsecured convertible senior notes on November 15, 2023.

● As part of our planned resubmission of our Biologics License Application ("BLA") for narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangiopathy ("TA-TMA"), we have submitted to FDA a formal statistical analysis plan to compare survival data from an already-identified external source. We continue to target an FDA approval decision on our resubmitted BLA in mid-2024.

● We have discontinued our Phase 3 ARTEMIS-IGAN clinical trial evaluating narsoplimab for the treatment of immunoglobulin A ("IgA") nephropathy based on the results of a pre-specified interim analysis, as announced in October 2023. Topline results showed that narsoplimab did not reach statistically significant improvement over placebo on the primary efficacy endpoint of reduction in proteinuria. In-depth analysis of the ARTEMIS-IGAN data are ongoing.

● An abstract with new and updated data from our Phase 2 clinical trial evaluating OMS906 in patients with paroxysmal nocturnal hemoglobinuria ("PNH") who have not previously been treated with a complement inhibitor has been selected for podium presentation at the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH"), upcoming in December. The presentation describes the clinically meaningful and statistically significant effects of OMS906 across all measured markers of hemolysis, including hemoglobin, lactate dehydrogenase ("LDH"), and red blood cell clone size in PNH patients.

● The Phase 2 "switch-over" trial evaluating OMS906 in PNH patients who have demonstrated an unsatisfactory response to treatment with the C5 inhibitor ravulizumab has completed enrollment. Reporting of data is expected later this year or early 2024.

● Andreas Grauer, M.D. joined Omeros as chief medical officer. In this role, Dr. Grauer is responsible for guiding all clinical activities globally for the company, including clinical development and operations, medical affairs, safety, and biometrics. A highly tenured physician, scientist and pharmaceutical leader, Dr. Grauer brings to Omeros over 20 years of industry experience across a broad range of therapeutic areas.

"Having discontinued our Phase 3 ARTEMIS-IGAN trial, we are closely examining the data to learn what happened and why so that we can apply the findings to the design and conduct of future renal clinical studies across our complement franchise," said Gregory A. Demopulos, M.D., Omeros’ chairman and chief executive officer. "Our primary focus is achieving regulatory approval and commercialization for our MASP-2 inhibitor narsoplimab to treat TA-TMA patients and driving our MASP-3 inhibitor OMS906, believed to be the premier alternative pathway target and drug, into multiple Phase 3 programs and completing clinical development as quickly as possible. The upcoming presentations at ASH (Free ASH Whitepaper) should help to focus others on the value of these programs – a TA-TMA approval will validate both narsoplimab and our other MASP-2 programs for which there are no predicates given Omeros’ broad patent position, while the multiple indications already validated by other alternative pathway inhibitors deliver a roadmap and are accretive to OMS906 and our MASP-3 platform. We expect that Omeros has the financial runway to capitalize on value-driving milestones for these programs, and we intend to extend that runway further through cost-containment measures and other means. Having secured substantial funding from NIDA for OMS527 and with the potential to lever a relatively small investment into a large value across our immuno-oncology platforms, our pipeline of clinical and earlier-stage assets remains robust with multiple opportunities to grow shareholder value."

Third Quarter and Recent Clinical Developments

● Recent developments regarding narsoplimab, our lead monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 ("MASP-2"), include the following:

o We continue to work towards the planned resubmission of our BLA for narsoplimab in TA-TMA. We have submitted to FDA a formal statistical plan for analysis of survival data available from an already-identified external source of TA-TMA patient data. In parallel, we continue to compile and revise the modules of our BLA for resubmission. Assuming favorable feedback on our formal plan for analysis of external survival data, we expect that the BLA could be completed and resubmitted within a timeframe that, allowing for the full FDA review period of six months, would result in FDA rendering an approval decision in mid-2024.

o In October 2023, we announced preliminary results of the pre-specified interim analysis of our Phase 3 ARTEMIS-IGAN trial evaluating narsoplimab for the treatment of IgA nephropathy. Topline results showed that narsoplimab did not reach statistically significant improvement over placebo on the primary endpoint of reduction in proteinuria assessed by 24-hour urine protein excretion at 36 weeks in the intent-to-treat population of 180 IgA nephropathy patients with baseline proteinuria above 2 grams per day. Although the narsoplimab-treated group reported substantial proteinuria improvement, the proteinuria improvement in the placebo group was substantially greater than in reported Phase 3 clinical trials assessing other agents for IgA nephropathy. Based on the absence of a statistically significant improvement, and as previously agreed with FDA, the ARTEMIS-IGAN clinical trial has been discontinued.

o An abstract detailing compassionate-use treatment with narsoplimab of 15 adult and pediatric patients with TA-TMA, 14 of whom had "high-risk" TA-TMA, has been accepted for presentation at the ASH (Free ASH Whitepaper) annual meeting to be held in December 2023. The poster will be presented by Dr. Marta Castelli, Department of Oncology and Hematology, University of Milan and Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.

o A manuscript describing the pulmonary and central nervous system benefits of MASP-2 blockade on symptoms and survival in well-established animal models of COVID-19-related acute respiratory distress syndrome ("ARDS") was published in October in the Journal of Infectious Diseases. Discussions are ongoing with the U.S. Government regarding development of narsoplimab for use in severe COVID-19 and other forms of ARDS.

● Recent developments regarding OMS1029, our long-acting, next-generation MASP-2 inhibitor, include:

o Dosing is completed in the first cohort of our ongoing Phase 1 multiple-ascending-dose ("MAD") study of OMS1029 in healthy subjects. In a single-ascending-dose Phase 1 clinical trial completed in early 2023, as in the ongoing MAD study, OMS1029 was well tolerated and no safety concerns were identified. Preliminary pharmacokinetic and pharmacodynamic ("PK/PD") data from that study showed dose-proportional exposure and sustained lectin pathway inhibition, consistent with once-quarterly intravenous or subcutaneous dosing. PK/PD data from the MAD study are expected in the first part of 2024. A Phase 2 program is slated to begin next summer in a larger market indication.

● Recent developments regarding OMS906, our lead monoclonal antibody targeting mannan-binding lectin-associated serine protease-3 ("MASP-3"), the key activator of the alternative pathway, include:

o Enrollment has been completed in our Phase 2 clinical trial evaluating OMS906 in PNH patients who have had an unsatisfactory response to the C5 inhibitor ravulizumab. The study has a "switch-over" design and enrolls PNH patients receiving ravulizumab, adds OMS906 to provide combination therapy with ravulizumab for 24 weeks, and then provides OMS906 monotherapy in patients who demonstrate a hemoglobin response with combination therapy. Data are expected to be shared publicly later this year or early next.

o Our clinical program evaluating OMS906 in patients with complement 3 glomerulopathy ("C3G") is also underway and is expected to begin enrolling C3G patients next month.

o We have initiated an extension study to assess the long-term safety and tolerability of OMS906 in patients with PNH. Enrolled patients who have completed one of our two Phase 2 PNH studies evaluating OMS906 will move directly into the extension study without interruption of treatment. Data from this study will support a planned BLA for OMS906 in PNH.

o Initiation of Phase 3 programs for OMS906 in PNH and C3G are targeted for the third quarter of 2024.

o An abstract with new and updated data from our Phase 2 study of OMS906 in treatment-naive PNH patients has been accepted for podium presentation at the upcoming ASH (Free ASH Whitepaper) annual meeting. The presentation describes the clinically meaningful and beneficial effects of OMS906 on hemoglobin with restoration of gender normal levels, on lactate dehydrogenase, and on red blood cell clone size in PNH patients.

o An abstract providing in vitro and in vivo mechanistic support for the clinical efficacy of OMS906 observed in treatment-naïve PNH patients will also be presented at the ASH (Free ASH Whitepaper) annual meeting.

o To date across all clinical studies with OMS906, the drug has been well tolerated and has demonstrated no safety signals of concern.

● Recent developments regarding OMS527, our phosphodiesterase 7 ("PDE7") inhibitor program focused on addictions and compulsive disorders as well as movement disorders, include:

o We continue to pursue development of our lead orally administered PDE7 inhibitor compound for the treatment of cocaine use disorder ("CUD"). This work was initiated at the request of, and is being performed in collaboration with, the National Institute on Drug Abuse ("NIDA"), part of the National Institutes of Health. The development efforts are supported by a three-year, $6.69 million grant from NIDA and is intended to support a preclinical cocaine interaction study and a randomized, placebo-controlled, inpatient clinical study evaluating the safety and effectiveness of OMS527 in patients with CUD. We expect the preclinical interaction study to begin in early 2024. Previously, a Phase 1 clinical trial of the study drug in healthy subjects was successfully completed.

o Together with collaborators at Emory University, we continue to evaluate the potential of our PDE7 inhibitors to treat levodopa-induced dyskinesias ("LID"). LID is caused by prolonged treatment with levodopa ("L-DOPA"), the most prescribed treatment for the over 10 million patients with Parkinson’s disease worldwide. LID is reported to affect approximately 50 percent of Parkinson’s patients who have been treated for five or more years with L-DOPA. The only approved treatment for LID is marginally effective and fraught with safety issues.

● Recent developments regarding OMIDRIA, our former ophthalmologic product used in cataract surgery on which we receive royalties on worldwide net sales by Rayner Surgical include the following:

o The Centers for Medicare and Medicaid Services ("CMS") issued its 2024 Hospital Outpatient Prospective Payment System final rule in October 2024. In that rule, CMS recommitted to separate payment for OMIDRIA in ambulatory surgery centers ("ASCs") throughout 2024. As mandated by Congress in this year’s Consolidated Appropriations Act, CMS, beginning January 1, 2025, will separately pay for OMIDRIA in both hospital outpatient departments and in ASCs until at least January 1, 2028.

Financial Results

Net loss was $37.8 million in the quarter ended September 30, 2023, or $0.60 per share, compared to a net loss in the prior year quarter of $17.5 million, or $0.28 per share. The increase in the current year quarter net loss was primarily attributable to an incremental $18.9 million gain in discontinued operations in the prior year quarter due to remeasurement of the contract royalty asset. Excluding the incremental gain, net loss for the prior year quarter would have been $36.4 million. Net loss from continuing operations was $51.7 million in the current quarter compared to a net loss of $54.8 million in the prior year quarter. Cash burn for the quarter ending September 30, 2023 was $31.0 million.

For the nine months ended September 30, 2023, our net loss was $108.8 million, or $1.73 per share compared to $81.3 million, or $1.30 per share, in the prior year period. Net loss from continuing operations for the nine months ended September 30, 2023 was $135.6 million compared to a loss of $136.0 million in the prior year period.

For the third quarter of 2023, we earned OMIDRIA royalties of $10.0 million on Rayner Surgical’s U.S. net sales of $33.3 million. This compares to earned royalties of $16.5 million during the third quarter of the prior year on U.S. net sales of $33.0 million. The difference in earned royalties reflects the decrease from 50 percent to 30 percent in the base royalty rate applicable to U.S. net sales of OMIDRIA, which occurred in December 2022 upon achievement of the $200.0 million milestone payment event. The royalty rate applicable to any sales outside the U.S. remains unchanged at 15 percent. Royalties are recorded as a reduction of the OMIDRIA contract royalty asset on our balance sheet.

Total costs and expenses for the third quarter of 2023 were $48.2 million compared to $50.8 million for the third quarter of 2022. The decrease was primarily due to reduction in clinical trial costs. This reduction was partially offset by increases in selling, general and administrative expenses.

Interest expense during the third quarter of 2023 was $7.9 million compared to $4.9 million during the prior year quarter. The increase was due to interest on our OMIDRIA royalty obligation associated with the sale of a portion of our OMIDRIA royalty receivables, an arrangement which we entered into at the end of September 2022.

During the third quarter of 2023, we earned $4.4 million in interest and other income compared to $0.9 million in the prior year quarter. The increase was due to higher average balances available to invest and higher market interest rates in the current year quarter.

Net income from discontinued operations, net of tax, was $13.9 million, or $0.22 per share, in the third quarter of 2023 compared to $37.3 million, or $0.59 per share, in the third quarter of 2022. The decrease in the current year quarter was primarily attributable to an incremental $18.9 million gain in discontinued operations in the prior year quarter due to the remeasurement of the contract royalty asset.

As of September 30, 2023, we had $310.3 million of cash and short-term investments, all of which are held in our name, available for operations and debt service.

On November 15, 2023, the $95.0 million outstanding on the 2023 unsecured convertible senior notes will become due. We anticipate retiring the notes at maturity with available cash and investments.

Conference Call Details

Omeros’ management will host a conference call and webcast to discuss the financial results and to provide an update on business activities. The call will be held today at 1:30 p.m. Pacific Time; 4:30 p.m. Eastern Time.

For online access to the live webcast of the conference call, go to Omeros’ website at View Source

To access the live conference call via phone, participants must register at this link to receive a unique PIN. Once registered, you will have two options: (1) Dial in to the conference line provided at the registration site using the PIN provided to you, or (2) choose the "Call Me" option, which will instantly dial the phone number you provide. Should you lose your PIN or registration confirmation email, simply re-register to receive a new PIN.

A replay of the call will be made accessible online at View Source

On November 9, 2023 Omega Therapeutics, Inc. (Nasdaq: OMGA) ("Omega"), a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines, reported financial results for the third quarter ended September 30, 2023, and highlighted recent Company progress (Press release, Omega Therapeutics, NOV 9, 2023, View Source [SID1234637406]).

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"The promising initial data from our ongoing MYCHELANGELO I trial establish clinical proof for our pioneering OMEGA platform and support the potential of epigenomic controllers, our programmable mRNA candidates, as a new class of therapeutics," said Mahesh Karande, President and Chief Executive Officer of Omega Therapeutics. "We are thrilled to have clearly demonstrated the ability to site-specifically target and controllably modulate the expression of MYC in all eight patients evaluated in the initial two dose cohorts of the trial. MYC, considered a "holy grail" oncogene, is just the first of many broadly-implicated targets in oncology where an epigenomic controller may provide therapeutic value. Moreover, these data highlight the promise of precision epigenomic control to address a broad range of diseases."

Mr. Karande added, "In parallel, we have made tremendous progress advancing our pipeline, with recent and upcoming presentations of new preclinical data demonstrating the breadth and versatility of our platform capabilities at scientific and medical meetings this fall. We look forward to building on this growing body of data and delivering a new class of medicines to patients."

Recent Highlights and Key Anticipated Milestones

Development Pipeline and Platform

•
Reported promising preliminary safety, tolerability, pharmacokinetic and translational data from the ongoing MYCHELANGELO I clinical trial evaluating OTX-2002 (data cut-off date of September 18, 2023):
o
Data from the initial two dose level cohorts (n=8) from the monotherapy dose escalation portion of the Phase 1/2 study evaluating OTX-2002 in patients with hepatocellular carcinoma (HCC) and other solid tumors associated with the c-MYC (MYC) gene showed that all eight patients treated with OTX-2002 achieved

highly specific on-target genomic engagement, intended epigenetic state change and rapid, robust and durable downregulation of MYC expression.
o
OTX-2002 was generally well tolerated at both dose levels, with no dose-limiting toxicities. Consistent dose-dependent pharmacokinetics were observed, and no drug accumulation was observed following repeat doses.
o
These data represent the first-known clinical observation of pre-transcriptional gene modulation using a programmable epigenomic mRNA candidate and establish clinical proof-of-platform.
o
Based on these encouraging data, OTX-2002 continues to advance in monotherapy dose escalation and the Company is actively evaluating patients with HCC in Cohort 3. Omega expects to report updated clinical data from monotherapy dose escalation in the first half of 2024.
o
The Company is planning to initiate expansion cohorts in monotherapy and in combination settings with standard of care agents mid-2024.
•
Presented new preclinical data supporting the potential of OTX-2101 for the treatment of non-small cell lung cancer (NSCLC) at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper):
o
The combination of a MYC-targeting epigenomic controller with immune checkpoint or EGFR inhibitors significantly enhanced anti-tumor activity in multiple preclinical models of NSCLC.
o
Omega continues to advance OTX-2101 in Investigational New Drug (IND)-enabling studies.
•
Presented preclinical proof-of-concept data for CXCL 1-8 program at the International mRNA Health Conference:
o
New preclinical data demonstrate the ability of the Company’s CXCL 1-8-targeting epigenomic controller to multiplex and specifically modulate gene expression of the multigenic locus in multiple models of inflammatory disease.
o
Omega has completed lead optimization activities for this program, including demonstration of in vivo proof-of-concept efficacy. The CXCL 1-8-targeting epigenomic controller has potential in multiple inflammatory indications including neutrophilic asthma, acute respiratory distress syndrome (including COVID-19-related), dermatological and rheumatological indications, and oncology, representing a potential franchise opportunity.

•
Announced upcoming presentation of preclinical proof-of-concept data on liver inflammation and fibrosis epigenomic controller programs at the American Association for the Study of Liver Diseases (AASLD) annual meeting: Omega will present new preclinical data from its hepatology programs in two posters at AASLD’s "The Liver Meeting" annual meeting, being held November 10-14, 2023, in Boston, Massachusetts.
o
One poster will highlight a CXCL 9-11-targeting epigenomic controller candidate for the treatment autoimmune hepatitis (AIH).
o
A second poster will highlight new in vitro and in vivo data demonstrating the ability of an investigational epigenomic controller to durably upregulate HNF4α expression to drive liver regeneration in preclinical models of fibrosis.

•
Continued to advance and expand OMEGA platform capabilities:
o
The Company continues to advance multiple epigenomic controller programs through discovery and lead optimization, and to further progress and

characterize its internal formulation and lipid nanoparticle (LNP) delivery technologies for the delivery of programmable mRNA therapeutics to the lung and other tissues.
Corporate

•
Further strengthened Board of Directors: In August, Omega announced the appointment of Chris Schade as Chairman of the Board. In addition, Michelle C. Werner, CEO of Alltrna and CEO-Partner at Flagship Pioneering, joined the Board, bringing with her over 20 years of biopharma experience spanning commercial and R&D responsibilities.
•
Named to BioSpace’s Best Places to Work 2024 report in small employer category: The annual report lists 60 U.S. operating employers that are recognized as the most sought-after in the industry by the life sciences community. Recognition by BioSpace is determined by input from company employees as well as voting from more than 3,000 life sciences professionals.

Third Quarter 2023 Financial Results

As of September 30, 2023, the Company had cash, cash equivalents and marketable securities totaling $89.3 million.

Research and development (R&D) expenses for the third quarter of 2023 were $16.5 million, compared to $20.7 million for the third quarter of 2022. The $4.2 million decrease in R&D expenses was primarily driven by decreases in external manufacturing costs and study costs, partially offset by an increase in facilities expense and, to a lesser extent, increases in personnel-related expenses and clinical development costs.

General and administrative (G&A) expenses for the third quarter of 2023 were $7.9 million, compared to $5.2 million for the third quarter of 2022. The $2.7 million increase in G&A expenses was primarily driven by an increase in facilities expense and, to a lesser extent, increases in professional and consulting fees, partially offset by a decrease in personnel-related expenses.

Net loss for the third quarter of 2023 was $22.2 million, compared to $25.8 million for the third quarter of 2022, driven predominantly by a decrease in R&D expenses.

On November 9, 2023 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported financial results for the third quarter ended September 30, 2023 (Press release, Nkarta, NOV 9, 2023, View Source [SID1234637405]).

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"Earlier this month, we announced bold plans for the future of Nkarta. This includes the expansion of our NK cell therapy pipeline into autoimmune disease, key anticipated updates in 2024, and the extension of our projected cash runway into 2026," said Paul J. Hastings, President and CEO of Nkarta. "Our pipeline now has three clinical-stage NK cell therapy programs, each increasing our opportunity for success. Our strategy for advancing these programs centers on stringent capital allocation, rapid execution, and business prioritization."

Hastings continued, "As we maintain our commitment to developing novel cell therapies for patients with cancer, we are also strongly encouraged by the prospect of NK cell-based therapies for patients with autoimmune disease. Early outcomes have been profound for patients treated with CD19-directed cell therapy in recent academic studies. Our aim is to replicate these remarkable, potentially disease-modifying benefits using NKX019, while still leveraging the advantages of NK cells. In addition to offering superior off-the-shelf accessibility, we aim to build on the safety profile of NK cell biology, the potential advantages of NK cell kinetics, and reduced need for lymphodepletion. Patients with severe autoimmune diseases need safe and novel therapies, and we look forward to initiating dosing in the clinical trial of NKX019 in patients with refractory lupus nephritis in the first half of 2024."

NKX019 in autoimmune disease

In October 2023, Nkarta announced the expansion of its pipeline to include autoimmune disease following the FDA clearance of its IND application for NKX019 in lupus nephritis (LN).
The expansion of NKX019 into an additional disease category is based on academic studies reporting durable complete responses to CD19-directed cell therapy in patients with severe, refractory autoimmune disease.
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 on Days 0, 7 and 14 following lymphodepletion (LD) with single agent cyclophosphamide (cy), an agent with an established safety profile in systemic lupus erythematosus (SLE) and LN.
Nkarta has partnered with Lupus Therapeutics, the clinical research affiliate of the Lupus Research Alliance, to accelerate development of NKX019 through select sites of the Lupus Clinical Investigators Network (LuCIN).
Nkarta plans to dose the first patient in the LN study in the first half of 2024.
Additional autoimmune diseases are being evaluated for potential clinical investigation with NKX019.
NKX101 in acute myeloid leukemia (AML)

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 patients that received NKX101 after LD comprising fludarabine and cytarabine (Flu/Ara-C), 4 of 6 achieved CR/CRi. Flu/Ara-C LD is expected to be the basis of NKX101 development moving forward.
Nkarta plans to present a poster at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2023 with follow-up data on the six patients from the June 2023 report that received NKX101 after Flu/Ara-C LD.
As previously announced, Nkarta successfully filed a manufacturing process change amendment with the FDA as part of ongoing scale-up and preparation for potential commercial manufacturing. After pausing for inventory buildup, patient enrollment resumed with material generated with the optimized manufacturing process.
As previously announced, Nkarta plans to present an update in the first half of 2024 that includes preliminary safety and response data from 12 to 20 additional patients that received NKX101 after Flu/Ara-C LD.
NKX019 in non-Hodgkin lymphoma (NHL)

In October 2023, Nkarta announced the opening of a new cohort in its Phase 1 study of NKX019 in r/r NHL. The new cohort introduces a compressed dosing schedule, where patients receive NKX019 doses on Days 0, 3 and 7 following LD with Flu/cy. In previous cohorts, NKX019 has been administered on Days 0, 7 and 14 following LD. The new dosing schedule is designed to intensify exposure to NKX019 in the first week after LD, when internal data suggest that NKX019 exposure is highest. The new cohort will target patients (n=6) with large B-cell lymphoma (LBCL), including those who have received prior CD19-directed CAR-T cell therapy.
Nkarta expects to announce preliminary data from the dose compression cohort in mid-2024.
In December 2022, Nkarta announced opening dose-expansion cohorts evaluating NKX019 monotherapy and NKX019 in combination with rituximab in patients with LBCL. Based on the preliminary results of NKX019 in the dose finding portion of the study, Nkarta is prioritizing the previously mentioned compressed dosing cohort and no longer enrolling patients in these cohorts.
Other Corporate Highlights

In October 2023, Nkarta announced cost containment measures, which included a reduction in force of approximately 10% of its workforce, a stringent cap on future headcount, planned centralization of operations to a single location, and early success in the optimization of Nkarta’s manufacturing platform.
Third Quarter 2023 Financial Highlights

As of September 30, 2023, Nkarta had cash, cash equivalents, restricted cash, and investments of $278.4 million.
Research and development (R&D) expenses were $22.2 million for the third quarter of 2023. Non-cash stock-based compensation expense included in R&D expense was $2.1 million for the third quarter of 2023.
General and administrative (G&A) expenses were $7.1 million for the third quarter of 2023. Non-cash stock-based compensation expense included in G&A expense was $2.2 million for the third quarter of 2023.
Net loss was $25.6 million, or $0.52 per basic and diluted share, for the third quarter of 2023. This net loss includes non-cash charges of $5.8 million that consisted primarily of share-based compensation and depreciation.
Financial Guidance

Nkarta expects its current cash and cash equivalents will be sufficient to fund its current operating plan into 2026.
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 (IL15) for greater persistence and activity without exogenous cytokine support.

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.

On November 9, 2023 Neogap Therapeutics, a company developing cell therapy for personalised cancer treatment, reported that it has strengthened its financial position through a new share issue of SEK 54 million, before issue costs, with the investment company Sciety and investment syndicate Sciety Venture Partners (Press release, Neogap Therapeutics, NOV 9, 2023, View Source,c3872193 [SID1234637404]). Alongside this, the company has received a grant of just over SEK 29 million from the European Innovation Council (EIC) Accelerator, a part of the EU’s Horizon Europe program.

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The positive comments from the EIC Accelerator evaluation notably underscore the unique nature and potential of Neogap’s treatment: "Neogap has a unique approach to a complete individualised therapy that unlike any other current therapies has curative potential in many types of solid cancer with low risk of serious side effects."

"These capital injections are a clear endorsement of the innovative spirit and dedicated team efforts that define Neogap’s work. The EU funding confirms our ambition to be a driving force in the field of cancer therapy. With these resources, we can continue our development work as planned, bringing us closer to our long-term objective – to improve treatment and increase survival for cancer patients," says Samuel Svensson, CEO of Neogap.

"We are delighted to once again invest in Neogap and thus be able to contribute to important advances in cancer treatment. The company has a unique approach that is based on the realisation that each cancer is unique and differs between different patients and tumours. By using proprietary algorithms for machine learning and patented technology to train the patient’s own T-cells to attack the cancer cells, the company develops a completely individualised treatment," says Andreas Lindblom, Managing Partner at Sciety.

Neogap’s personalised immunotherapy has the potential to tackle a variety of cancer types, with a primary focus on colorectal cancer, which accounts for approximately 10% of all cancer cases and is the second leading cause of death due to cancer. Leveraging its technologies, PIOR and EpiTCer, Neogap is developing personalised therapy strategies for each patient. This bespoke and targeted approach ensures that the therapy selectively attacks cancer cells and minimises impact on healthy tissue, which in turn contributes to a low risk of side effects.

Neogap’s ongoing phase I/II study primarily aims to demonstrate the treatment’s safety, but the company will also explore signs of treatment efficacy, including measurement of tumour growth.

On November 9, 2023 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported business highlights and financial results for the quarter ended September 30, 2023 (Press release, Monte Rosa Therapeutics, NOV 9, 2023, View Source [SID1234637403]).

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"This has been a pivotal time for Monte Rosa as we announced both our first clinical data and our first major strategic collaboration," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "We’re very excited about the clinical data for MRT-2359, our GSPT1-directed molecular glue degrader, and in particular the early signs of clinical activity in MYC-driven solid tumors. We’re equally excited to partner with Roche to enable and accelerate expansion of our QuEEN discovery engine to discover and develop molecular glues against targets previously considered impossible to drug for cancer and neurological diseases. We also completed a registered direct offering that, together with our ongoing pipeline prioritization efforts, is expected to extend our cash runway into the first half of 2026. We look forward to continuing to execute on our pipeline, including delivering Phase 2 interim data for MRT-2359 and Phase I healthy volunteer data for our immunology and inflammation-directed VAV1 and NEK7 programs."

THIRD QUARTER 2023 AND RECENT HIGHLIGHTS

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Announced interim clinical data from the ongoing MRT-2359 Phase 1/2 study demonstrating favorable pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles in heavily pre-treated patients with MYC-driven solid tumors, including lung cancers and high-grade neuroendocrine tumors. MRT-2359 showed evidence of tumor size reductions, including partial responses, in heavily pretreated patients with biomarker-positive tumors. Optimal PD modulation of GSPT1 in peripheral blood mononuclear cells and tumor tissue biopsies was observed at all dose levels, consistent with its designed activity based on preclinical studies.
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Entered into a strategic collaboration and licensing agreement with global healthcare leader Roche to discover and develop MGDs against targets in cancer and neurological diseases. Under the terms of the agreement, Monte Rosa Therapeutics will receive an upfront payment of $50 million, and is eligible to receive future preclinical, clinical, commercial and sales milestone payments that could exceed $2 billion, as well as tiered royalties.

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Completed a $25 million registered direct offering, priced at-the-market under Nasdaq rules, with a life sciences-dedicated investor.
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Presented preclinical data at the American College of Rheumatology (ACR) Convergence Annual Meeting demonstrating the potential of MRT-6160, a VAV1-targeting MGD, to treat immunological and inflammatory diseases. The data show that MRT-6160 attenuated disease progression in a murine collagen-induced arthritis (CIA) model.
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Appointed Anthony M. Manning, Ph.D., to the Company’s Board of Directors. Dr. Manning is a highly accomplished drug discovery leader in the field of autoimmune and inflammatory diseases.
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Discontinued sickle cell disease program to prioritize internal efforts on ongoing clinical-, Investigational New Drug (IND)- and lead optimization-stage programs.

UPCOMING MILESTONES

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The Company now expects to release the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study in Q2 2024.
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On track for planned IND submission for MRT-6160 in the first half of 2024.
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The Company expects to nominate a development candidate for its NEK7 preclinical program in Q1 2024.
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The Company expects to nominate a development candidate for its CDK2 preclinical program in 2024.

THIRD QUARTER 2023 FINANCIAL RESULTS

Research and Development (R&D) Expenses: R&D expenses for the third quarter of 2023 were $28.3 million, compared to $21.3 million for the third quarter of 2022. These increases were driven by the successful achievement of key milestones in our R&D organization, including the advancement of MRT-2359 in the clinic, the progression of our preclinical pipeline, and the continued development of the Company’s QuEEN platform for discovery efforts. The increase in R&D expenses was driven by increased headcount and laboratory-related expenses to achieve these milestones. Non-cash stock-based compensation constituted $2.3 million of R&D expenses for Q3 2023, compared to $1.7 million in the same period in 2022.

General and Administrative (G&A) Expenses: G&A expenses for the third quarter of 2023 were $8.7 million compared to $7.0 million for the third quarter of 2022. The increase in G&A expenses was a result of increased headcount and expenses in support of the company’s growth and operations. G&A expenses included non-cash stock-based compensation of $2.2 million for the third quarter of 2023, compared to $1.5 million for the same period in 2022.

Net Loss: Net loss for the third quarter of 2023 was $34.9 million, compared to $27.3 million for the third quarter of 2022.

Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of September 30, 2023, were $183.0 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $207.6 million as of June 30, 2023. The decrease of $24.6 million was primarily related to cash used to fund operations. The September 30, 2023, cash and equivalents balance does not include the $50 million upfront payment from Roche or the approximately $25 million proceeds from the registered direct offering, which were received after the end of Q3 2023.

The company expects its cash and cash equivalents, including proceeds from the Roche collaboration, will be sufficient to fund planned operations and capital expenditures into the first half of 2026.

About MRT-2359

MRT-2359 is a potent, selective and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

About MRT-6160

MRT-6160 is a potent, highly selective, and orally bioavailable investigational degrader of VAV1, which in our in vitro studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T-and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple autoimmune indications, such as multiple sclerosis, rheumatoid arthritis, and dermatological disorders. Preclinical studies demonstrate MRT-6160 inhibits disease progression in in vivo autoimmunity models.