On November 9, 2022 Omeros Corporation (Nasdaq: OMER), a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market as well as orphan indications targeting inflammation and immunologic diseases, including complement-mediated diseases and cancers, reported recent highlights and developments as well as financial results for the third quarter ended September 30, 2022, which include (Press release, Omeros, NOV 9, 2022, View Source [SID1234623549]):

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For the quarter ended September 30, 2022, we earned royalties of $16.5 million on net sales of our former ophthalmology product OMIDRIA. Royalties earned in the quarter represent 50 percent of net sales of OMIDRIA by Rayner Surgical, Inc. (Rayner), which purchased our ophthalmology assets in December 2021. Rayner’s U.S. net sales of OMIDRIA were $33.0 million for the third quarter of 2022.
Net loss in 3Q 2022 was $17.5 million, or $0.28 per share, which included $4.6 million of non-cash expenses, or $0.07 per share. This compares to a net loss of $22.7 million, or $0.36 per share for the prior year quarter, which included $6.4 million of non-cash expenses, or $0.10 per share.
On September 30, 2022, we sold to DRI Healthcare Acquisitions LP (DRI) an interest in a portion of our future OMIDRIA royalty receivables for a cash purchase price of $125.0 million. The purchased royalty interest entitles DRI to receive royalty payments on OMIDRIA net sales between September 1, 2022 and December 31, 2030, up to the amount of maximum caps established for each annual period. The maximum aggregate payout DRI is entitled to receive is $188.4 million.
At September 30, 2022, we had $221.0 million of cash, cash equivalents and short-term investments.
As announced yesterday, we received the decision by FDA’s Office of New Drugs (OND) denying our appeal of the complete response letter (CRL) issued earlier by FDA concerning the biologics license application (BLA) for narsoplimab in hematopoietic stem cell transplant-associated microangiopathy (TA-TMA). Although our request for immediate resubmission and labeling discussions was denied, the decision proposes a path forward for resubmission of the BLA based on survival data from the completed pivotal trial versus a historical control group, with or without an independent literature analysis.
In November 2022, the Centers for Medicare and Medicaid Services (CMS) issued its final Hospital Outpatient Prospective Payment and Ambulatory Surgical Center Payment Systems rule for calendar year 2023. The rule confirms that for calendar year 2023 CMS will continue to pay separately for OMIDRIA when used in ambulatory surgical centers.
"FDA’s decision on our CRL appeal request provides paths forward that are based on a comparison of patient survival in our pivotal trial to historical survival data in TA-TMA and to response data in the literature. Together with our regulatory and legal advisors, we are assessing potential next steps and look forward to working with the Agency to approve narsoplimab as quickly as possible," said Gregory A. Demopulos, M.D., Omeros’ chairman and chief executive officer. "Also heading into 2023, we have established financial flexibility with our royalty monetization transaction, which could be further strengthened by our receipt of the $200-million OMIDRIA-related milestone payment. From our clinical trials, throughout the coming year we anticipate data from our MASP-3 inhibitor OMS906 in PNH and C3 glomerulopathy beginning in the first quarter, from our Phase 1 program for our long-acting MASP-2 inhibitor in the second quarter and, in mid-year, from our narsoplimab Phase 3 trial in IgA nephropathy. We also expect news from our OMS527 PDE7 inhibitor and immuno-oncology programs. All of these assets are rapidly advancing – collectively representing significant opportunities and substantial enterprise 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) in advanced clinical programs for the treatment of TA-TMA, immunoglobulin A (IgA) nephropathy, atypical hemolytic uremic syndrome (aHUS) and severely ill COVID-19 patients, include the following:
On October 18, 2021, we announced the receipt of a CRL from FDA indicating that the BLA for narsoplimab in TA-TMA could not be approved as submitted. Following additional interactions with FDA regarding the BLA we submitted a Formal Dispute Resolution Request, in June 2022, appealing the issuance of the CRL to a higher level within FDA, in this case OND, and requesting that OND direct the review division to accept a Class 1 resubmission of the BLA and to commence labeling discussions immediately thereafter. In November 2022, we received OND’s decision denying our appeal. Although our request for immediate resubmission and labeling discussions was denied, the decision proposes a path forward for the resubmission of the BLA based on survival data from the completed pivotal trial versus a historical control group. Specifically, the decision proposes the resubmission of the narsoplimab BLA including a comparison of the existing response data from the completed pivotal trial to a threshold derived from an independent literature analysis and evidence of increased survival from patients in the pivotal trial compared to an appropriate historical control group. It also notes that persuasive evidence of superior survival versus a well-matched historical control group could be sufficient even in the absence of the independent literature analysis. The specific approach to any resubmission and its details would be determined through discussion with the review division.
Enrollment in our Phase 3 ARTEMIS-IGAN trial continues to progress toward an anticipated readout of 9-month data on proteinuria by mid-next year.
A case report describing the successful treatment of an adult patient with recurrent IgA nephropathy under compassionate use was presented at the American Society of Nephrology’s kidney week congress held last week in Orlando, Florida. The poster presentation is entitled Narsoplimab Treatment for Recurrent IgA Nephropathy Stabilized eGFR and Proteinuria.
A poster presentation describing the design of our open-label Phase 2 study evaluating efficacy and safety of narsoplimab in pediatric patients with high-risk TA-TMA will be presented at the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) to be held in December 2022 in New Orleans, Louisiana.
In September 2022, results of the narsoplimab treatment arm of the I-SPY COVID-19 adaptive platform trial sponsored by Quantum Leap Healthcare Collaborative were announced. Although the narsoplimab treatment arm was terminated prior to accrual of the maximum of 125 patients, analysis in the randomized patient population showed that the addition of narsoplimab to treatment of critically ill patients with COVID-19 reduces the mortality risk (hazard ratio [HR]=0.81, with probability [HR <1] equal to 0.77). In approximately half of the patients who died in the narsoplimab group, narsoplimab was not given or was prematurely stopped, with those patients dying 9 to 35 days later. Neither the trial’s futility nor graduation criteria had been met in the analysis of the randomized population at the time the narsoplimab arm was terminated; however, Quantum Leap’s data monitoring committee terminated the narsoplimab treatment arm on the basis of analysis in a population of pre-consented patients in which substantial imbalance was detected, resulting in a marked bias against the narsoplimab arm.
Recent developments regarding OMS906, our lead monoclonal antibody targeting MASP-3, the key activator of the alternative pathway, and OMS1029, the company’s long-acting, next-generation MASP-2 inhibitor, include the following:
We expect soon to begin enrolling patients in a Phase 1b clinical trial evaluating OMS906 in patients with paroxysmal nocturnal hemoglobinuria (PNH) who have had an unsatisfactory response to the C5 inhibitor ravulizumab. Regulatory submissions and site selection are also progressing on a planned expansion of clinical programs designed to evaluate OMS906 in treatment-naïve PNH patients, patients with complement 3 (C3) glomerulopathy and, potentially, patients with one or more related indications. Initial efficacy data from these open-label studies are targeted for availability in early 2023.
A poster presentation describing the results of a Phase 1 single-ascending-dose clinical trial of OMS906 in normal human volunteers will be featured at the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) to be held in December 2022 in New Orleans, Louisiana.
A Phase 1 clinical trial assessing safety, tolerability and pharmacokinetics/pharmacodynamics (PK/PD) of OMS1029 in healthy subjects is underway, with dosing of the first three of six cohorts in the single-ascending-dose study now complete. Dosing of OMS1029 is expected to be once-monthly to once-quarterly by subcutaneous or intravenous administration. This next-generation MASP-2 inhibitor is intended as complementary to narsoplimab, enabling us to pursue both acute and chronic indications and to provide a significant benefit of dosing convenience to patients.
Financial Results

On September 30, 2022, we sold to DRI an interest in a portion of our future OMIDRIA royalty receivables in exchange for $125.0 million in cash consideration. DRI is entitled to receive royalties on OMIDRIA net sales between September 1, 2022 and December 31, 2030, up to the amount of a fixed annual cap. DRI receives payment of royalties monthly, as received from Rayner, up to the amount of a prorated monthly cap amount before we receive any royalty proceeds. DRI is not entitled to carry-forward nor recoup any shortfall if the royalties paid by Rayner for an annual period are less than the cap amount for the applicable calendar year. Additionally, DRI has no recourse to or security interest in our assets other than our OMIDRIA royalty receivables. We retain all royalty receipts in excess of the respective cap in any given year. The maximum aggregate payout DRI is entitled to receive is $188.4 million which, if fully paid, is an effective interest rate of 9.4%. The maximum amount payable for the remainder of 2022 is $1.7 million. The maximum amount payable in 2023 is $13.0 million. Assuming the maximum amount is paid each year, DRI will recoup the $125 million purchase price in August 2028.

During the third quarter of 2022, we earned royalties of $16.5 million on sales of OMIDRIA, which were recorded as a reduction from the OMIDRIA contract royalty asset. We also recorded $37.3 million of income in discontinued operations, primarily representing interest income and remeasurement adjustments to the OMIDRIA contract royalty asset.

Total costs and expenses for the third quarter of 2022 were $50.8 million compared to $39.8 million for the third quarter of 2021. The increase was primarily due to the manufacturing of narsoplimab drug substance in the third quarter of 2022 for future commercial and clinical use.

Net loss was $17.5 million in the third quarter of 2022, or $0.28 per share, which included $4.6 million of non-cash expenses, or $0.07 per share. This compares to a net loss of $22.7 million, or $0.36 per share, including $6.4 million of non-cash expenses, or $0.10 per share, in 3Q 2021.

As of September 30, 2022, we had $221.0 million of cash, cash equivalents and short-term investments.

Conference Call Details

To access the live conference call via phone, participants must register at the following link to receive a unique PIN: https://register.vevent.com/register/BI4363ad5bbf154eef81c3be16f4e47738. 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.

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

On November 9, 2022 Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), reported financial results for the three months ended September 30, 2022 and provided an update on key corporate milestones (Press release, Lexicon Pharmaceuticals, NOV 9, 2022, View Source [SID1234623548]).

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"Our mid-cycle review meeting with the FDA was held this week for our NDA for sotagliflozin for the treatment of heart failure, which remains on track for its PDUFA action date in May 2023," said Lonnel Coats, Lexicon’s chief executive officer. "This past weekend, important data for sotagliflozin were presented at two major medical conferences, notably including an oral presentation at the American Heart Association Scientific Sessions 2022 on reduced cardiovascular mortality and hospital readmissions for heart failure at 30- and 90-days post discharge in patients hospitalized for worsening heart failure in the SOLOIST-WHF trial."

"This coming Monday, final data from our successful RELIEF-DPN-1 study of LX9211 in painful diabetic neuropathy will be presented at the 16th Annual Pain Therapeutics Summit in Washington, D.C., which we will follow with a conference call discussing the results and their importance in an area of significant unmet need," Mr. Coats continued. "Finally, we completed enrollment earlier this quarter in our RELIEF-PHN-1 study of LX9211 in post-herpetic neuralgia, from which we expect to report top-line data before year-end."

Third Quarter Highlights

Sotagliflozin

•The U.S. Food and Drug Administration (FDA) accepted for review and filed Lexicon’s New Drug Application (NDA) for sotagliflozin for the treatment of heart failure. The FDA assigned a standard review for the NDA filing with a Prescription Drug User Fee Act (PDUFA) target action date in May 2023.
•Two posters were presented at the 70th annual European Society of Cardiology Congress, highlighting protein expression analyses comparing sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, with a selective SGLT2 inhibitor in cell-based models relative to inflammation and thrombosis.
◦The first poster, "Sotagliflozin, a Dual SGLT1/2 Inhibitor, Reduced Expression of Neutrophil Degranulation Proteins During Endothelial Dysfunction Compared with a Selective SGLT2 Inhibitor," concluded that the favorable effects of sotagliflozin on mechanisms of inflammation have implications for ischemic disease, including myocardial infarction and stroke.
◦The second poster, "Sotagliflozin, a Dual SGLT1/2 Inhibitor, Reduced Expression of Platelet Activators During Endothelial Dysfunction Compared to Empagliflozin," concluded that the effects of dual SGLT1 and SGLT2 inhibition on platelet activity may have implications for reduced atherothrombotic risk.
•A manuscript entitled "Metabolic, Intestinal, and Cardiovascular Effects of Sotagliflozin Compared with Empagliflozin in Patients with Type 2 Diabetes: A Randomized, Double-Blind Study" was published in the September issue of the journal Diabetes Care. Results from the study showed significant differences between the agents with respect to certain incremental incretin levels following meals, particularly at breakfast. Sotagliflozin significantly reduced postprandial glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) and significantly increased glucagon-

like peptide 1 (GLP-1), in each case relative to empagliflozin and consistent with sotagliflozin’s inhibition of intestinal SGLT-1. The favorable changes in these measures were noted in the manuscript as having potential implications for cardiovascular disease.

LX9211

•A poster was presented and an oral presentation was given at the PAINWeek 2022 National Conference on Pain Management. The poster and presentation, each titled "LX9211, a Novel Therapeutic Approach to Treatment of Neuropathic Pain," described the mechanism of action of LX9211’s novel target, adaptor-associated protein kinase 1 (AAK1), as well as results from multiple preclinical models of neuropathic pain after treatment with LX9211.
•A poster was presented at the IASP World Congress on Pain, titled "Efficacy, Safety, and Pharmacokinetics of LX9211 in the Treatment of Diabetic Peripheral Neuropathic Pain (RELIEF-DPN-1)," outlining the study design, baseline patient characteristics, and positive results of the primary endpoint of the study.

Public Offering and Concurrent Private Placement

•Lexicon completed a public offering and concurrent private placement of common stock, with net proceeds to the company of $94.3 million.

Third Quarter 2022 Financial Highlights

Research and Development (R&D) Expenses: Research and development expenses for the third quarter of 2022 decreased to $10.6 million from $15.7 million for the corresponding period in 2021, primarily due to lower clinical external research expenses and professional and consulting costs.

Selling, General and Administrative (SG&A) Expenses: Selling, general and administrative expenses for the third quarter of 2022 increased to $12.6 million from $7.3 million for the corresponding period in 2021, primarily due to increases in salaries and benefits, professional and consulting costs and marketing costs relating to preparations for the commercial launch of sotagliflozin.

Net Loss: Net loss for the third quarter of 2022 was $23.4 million, or $0.13 per share, as compared to a net loss of $23.1 million, or $0.16 per share, in the corresponding period in 2021. For the third quarters of 2022 and 2021, net loss included non-cash, stock-based compensation expense of $2.6 million and $2.7 million, respectively.

Cash and Investments: As of September 30, 2022, Lexicon had $136.2 million in cash and investments, as compared to $86.7 million as of December 31, 2021

Conference Call and Webcast Information

Lexicon management will hold a live conference call and webcast today at 5:00 pm ET / 4:00 pm CT to review its financial and operating results and to provide a general business update. The dial-in number for the conference call is 888-886-7786 and the conference ID for all callers is 70766912. The live webcast and replay may be accessed by visiting Lexicon’s website at www.lexpharma.com/events. An archived version of the webcast will be available on the website for 14 days.

On November 9, 2022 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported financial results for the third quarter ended September 30, 2022 (Press release, Repare Therapeutics, NOV 9, 2022, View Source [SID1234623547]).

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"Our focus in the third quarter has remained on execution of our pipeline of programs including RP-6306, our first-in-class, oral PKMYT1 inhibitor currently being evaluated in the Phase 1 MYTHIC, MAGNETIC, and MINOTAUR studies. We look forward to reporting data for RP-6306 in the first half of 2023 as we continue to execute on this novel program," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "Based on promising preclinical data released at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium in October 2022, Repare is working with clinical investigators to initiate clinical testing of a new carboplatin combination with RP-6306 in 2023."

"This quarter, after HSR clearance, we closed our worldwide license and collaboration agreement with Roche for the development and commercialization of camonsertib (also known as RP-3500). We recognize the significant collaborative efforts by Roche and our team in completing a swift and efficient regulatory and operational transfer of this program, while we continue to provide ongoing support for the TRESR and ATTACC trials into 2023. In connection with this agreement, Repare received a $125 million upfront payment in July 2022 and may expect to receive up to $55 million in potential near-term payments."

"We also made important progress in advancing RP-2119, our polymerase theta inhibitor, with ongoing IND-enabling studies and we expect to initiate clinical trials next summer. We are also preparing to conduct further IND-enabling studies for an additional small molecule in the first half of 2023 as we look to another substantial year ahead."

Third Quarter 2022 Review and Operational Updates:

Evaluating RP-6306, a first-in-class, oral PKMYT1 inhibitor as a monotherapy and in combinations in multiple Phase 1 studies.
Repare continues to advance Phase 1 clinical trials evaluating RP-6306 as a monotherapy (MYTHIC), as well as in combinations with gemcitabine (MAGNETIC), FOLFIRI (MINOTAUR), and camonsertib (MYTHIC), each for the treatment of molecularly selected advanced solid tumors.
Initial Phase 1 clinical data readout for RP-6306 is expected in the first half of 2023.
Based on promising preclinical data released at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium in October 2022, Repare is working with clinical investigators to initiate clinical testing of a new carboplatin combination with RP-6306 in 2023. Repare demonstrated that the PKMYT1 inhibitor RP-6306 synergized with carboplatin in multiple CCNE1 high/amplified cellular models to induce an increase in DNA damage, which led to increased cell death compared to either agent alone. The combination of RP-6306 and carboplatin induced profound tumor regression in the OVCAR3 xenograft model and was well tolerated with no additional suppression of red blood cells or neutrophils.
Preclinical data from RP-6306 was published in Journal of Medicinal Chemistry in July 2022. The article, entitled "Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306", is available on the Company website under Scientific References.
Advancing camonsertib, a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase) for the treatment of tumors with specific synthetic lethal genomic alterations, in partnership with Roche.
Under the agreement with Roche, Roche assumed the development of camonsertib with the potential to expand development into additional tumor indications and multiple combination studies.
Repare will continue to provide ongoing support for the TRESR and ATTACC trials into 2023.
In connection with this agreement, Repare received a $125 million upfront payment in July 2022. Repare is eligible to receive up to an additional $1.172 billion in potential development, regulatory, commercial and sales milestones, including up to $55 million in potential near-term payments, and royalties on global net sales ranging from high-single-digits to high-teens.
Advancing IND-enabling studies for RP-2119, Repare’s Polθ inhibitor, and plan to initiate clinical trials in the summer of 2023.
Repare also expects to initiate IND-enabling studies in the first half of 2023 for an additional small molecule against an undisclosed target.
Third Quarter 2022 Financial Results:

Cash and cash equivalents and marketable securities: Cash and cash equivalents and marketable securities as of September 30, 2022 were $370.4 million, which Repare believes will be sufficient to fund planned operations into 2026.
Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were $31.2 million and $89.2 million for the three and nine months ended September 30, 2022, respectively, as compared to $25.4 million and $62.1 million for the three and nine months ended September 30, 2021. The increase in R&D expenses for the three- and nine-month periods were primarily due to an increase in development activities related to the advancement of the RP-6306 program and the RP-2119 IND-enabling studies; an increase of personnel-related costs, including share-based compensation, for increased headcount in support of discovery and development activities; and other research and development costs. Camonsertib costs increased year over year as a result of higher development costs in relation to the advancement of the program, but decreased quarter over quarter following the transfer of CMC related activities to Roche pursuant to the collaboration agreement.
General and administrative (G&A) expenses: G&A expenses were $8.0 million and $24.6 million for the three and nine months ended September 30, 2022, respectively, as compared to $6.6 million and $18.6 million for the three and nine months ended September 30, 2021. The increase in G&A expenses for the three- and nine-month periods were primarily due to an increase in personnel related costs, including share-based compensation; an increase in professional fees associated with the Roche collaboration agreement and the establishment of our at-the-market (ATM) offering, as well as timing of audit and SOX compliance efforts, partially offset by a decrease in our D&O insurance premium.
Net income (loss): Net income was $75.5 million, or $1.71 diluted earnings per share, or EPS, and $2.6 million, or $0.06 diluted EPS, for the three and nine months ended September 30, 2022, respectively, and net loss was $30.9 million, or $0.83 diluted loss per share, and $78.6 million, or $2.12 diluted loss per share, for the three and nine months ended September 30, 2021, respectively.
About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.

On November 9, 2022 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, reported financial results for the third quarter ended September 30, 2022 (Press release, Nkarta, NOV 9, 2022, View Source [SID1234623546]).

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"The third quarter marked significant progress as we continue to treat patients across our two lead clinical programs," said Paul J. Hastings, President and CEO of Nkarta. "We recently completed the first cycle of treatment for patients in the NKX019 monotherapy dose escalation cohort and look forward to announcing new clinical data by year-end, including data from responding patients reported in the last update. We’ve also opened enrollment in multiple dose expansion cohorts, where we intend to build on our prior experience with NKX019 in patients with autologous CAR T naïve, relapsed/refractory (r/r) LBCL, while simultaneously investigating activity in patients with LBCL who have previously received autologous CAR T. We will also explore NKX019 in combination with rituximab, regardless of prior CAR T treatment. NKX101 continues to enroll patients in monotherapy dose escalation, and we have updated the timing of NKX101 data in r/r AML to the first half of next year. We are continuing our mission to bring our allogeneic, off-the-shelf cell therapies to patients in outpatient and community oncology settings, enabling convenient multi-cycle treatment and broad access."

Anticipated Clinical Milestones

Nkarta plans to present additional clinical data from its ongoing Phase 1 clinical trial of NKX019 by year-end 2022 as part of a company-hosted announcement.
Nkarta plans to present additional clinical data from its ongoing Phase 1 clinical trial of NKX101 in the first half of 2023. Nkarta updated this timing from year-end 2022 in order to collect a more robust and interpretable data set from a heavily pre-treated and heterogenous patient population.
The data updates for NKX019 and NKX101 are expected to include safety and activity data from patients in the dose escalation cohorts who receive the 3-dose monotherapy treatment at the higher 1.5 billion CAR NK cell dose, durability of response in patients who were in response as of the April 2022 data cut-off, and safety and activity data from patients in the dose escalation cohorts who may have received one or more additional cycles of CAR NK cell therapy, including consolidation therapy.
NKX019 Dose Expansion Cohorts

Nkarta recently opened enrollment in the dose expansion portion of its Phase 1 clinical trial of NKX019. This dose expansion will investigate for the first time NKX019 as combination therapy with rituximab, an anti-CD20 monoclonal antibody, in patients with r/r non-Hodgkin lymphoma, as well as NKX019 as monotherapy in patients with large B-cell lymphoma (LBCL) who previously received autologous CD19 CAR T therapy. The dose expansion will also further investigate NKX019 as monotherapy in patients with LBCL who have not previously received autologous CD19 CAR T therapy.
Owing to the recent start of patient enrollment, data from the dose expansion cohorts are not expected to be announced in the NKX019 clinical update planned for 2022.
NKX101 Clinical Data – April 2022

On April 25, 2022, Nkarta reported preliminary data from its Phase 1 clinical trial evaluating NKX101, an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses NK cells engineered to target NKG2D ligands on cancer cells, as a multi-dose, multi-cycle monotherapy in patients with r/r acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (MDS). As of data cut-off on April 21, 2022, 21 patients had been enrolled and dosed.
Three of five patients with heavily pre-treated AML treated at the higher dose levels in a three-dose regimen achieved a complete response (60% CR) with hematologic recovery, with two of the three responses MRD (measurable residual disease) negative.
NKX101 was well tolerated. No dose-limiting toxicities were observed. No cytokine release syndrome (CRS), graft-versus-host disease (GvHD), or immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. The most common higher-grade adverse events were myelosuppression and infection, which are common in this patient population following lymphodepletion.
NKX019 Clinical Data – April 2022

On April 25, 2022, Nkarta reported preliminary data from its Phase 1 clinical trial evaluating NKX019, an allogeneic, cryopreserved, off-the-shelf cancer immunotherapy candidate that uses NK cells engineered to target the B-cell antigen CD19, as a multi-dose, multi-cycle monotherapy in patients with r/r B-cell malignancies. As of data cut-off on April 21, 2022, 13 patients had been enrolled and dosed.
Three of six patients treated at the higher dose level in a three-dose regimen showed a complete response (50% CR), including one patient with aggressive large B cell lymphoma (LBCL) and one patient with mantle cell lymphoma (MCL).
NKX019 was well tolerated. No dose-limiting toxicities were observed. No CRS, GvHD, or neurotoxicity (ICANS) was observed. The most common higher-grade adverse events were myelosuppression, which is common in this patient population following lymphodepletion.
SITC 2022

In November 2022, Nkarta presented preclinical data from its engineered NK cell platform in two posters at the annual meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper).
Poster #902, "NKX019, an Off-the-Shelf CD19 CAR-NK Cell, Mediates Improved Anti-Tumor Activity and Persistence in Combination with CD20-Directed Therapeutic mAbs," presents preclinical data on the improved anti-tumor activity demonstrated by the combination of NKX019 and a CD20-directed monoclonal antibody (mAb). This combination showed superior tumor cell killing compared to that of NKX019 and either mAb alone. Each agent was capable of direct killing of tumor cells, and when combined they further acted through ADCC, or antibody dependent cellular cytotoxicity. ADCC is a mechanism of immune defense whereby immune cells such as NK cells can recognize and kill tumor cells whose surface antigens are coated with antibodies. ADCC is one of several mechanisms by which NK cells are known to kill tumor cells.
Poster #381, "Large-Scale Expansion and Engineering of Human NK Cells Sourced from Peripheral Blood Versus Umbilical Cord Blood," presents data on the use of Nkarta’s proprietary NKSTIM cell line to expand NK cells in support of potential large-scale commercial production of therapeutic CAR NK cells. NK cells derived from the healthy-donor peripheral blood were expanded over 250 billion-fold while maintaining chromosomal integrity and potency against multiple tumor cell models, and compared favorably to NK cells derived from cord blood. Cell populations capable of superior expansion and native potency could be identified in adult donor-derived NK cells, allowing the potential selection of optimal donors and cell populations for enhanced CAR NK cell production.
Other Corporate Highlights

In August 2022, Nkarta signed amended lease agreements for its future cell therapy manufacturing facility and company headquarters and for its existing facilities. The amendments provide for approximately $15 million of additional tenant improvement allowances for the future facility, increase the rent for the future facility, and increase the rent and term of the lease for some of Nkarta’s existing facilities. These allowances are in addition to the tenant improvement allowances of $25.2 million included in the original lease agreement for the future facility. Nkarta’s facilities are located in South San Francisco, California.
Third Quarter 2022 and Recent Financial Highlights

Cash and Cash Equivalents: As of September 30, 2022, Nkarta had cash, cash equivalents, restricted cash, and short-term investments of $395.1 million.
R&D Expenses: Research and development (R&D) expenses were $23.4 million for the third quarter of 2022. Non-cash stock-based compensation expense included in R&D expense was $1.9 million for the third quarter of 2022.
G&A Expenses: General and administrative (G&A) expenses were $6.8 million for the third quarter of 2022. Non-cash stock-based compensation expense included in G&A expense was $2.4 million for the third quarter of 2022.
Net Loss: Net loss was $28.3 million, or $0.58 per basic and diluted share, for the third quarter of 2022. This net loss includes non-cash charges of $5.9 million that consisted primarily of share-based compensation of $4.4 million.
Financial Guidance

Nkarta expects its current cash and cash equivalents will be sufficient to fund its current operating plan into 2025.
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 membrane-bound form of interleukin-15 (IL15) for greater persistence and activity without exogenous cytokine support. To learn more about the NKX101 clinical trial in adults with AML or MDS, please visit ClinicalTrials.gov.

About NKX019
NKX019 is an allogeneic, cryopreserved, off-the-shelf cancer 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 tumor 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 and malignant B cells, and it is a validated target for B cell cancer therapies. To learn more about the NKX019 clinical trial in adults with advanced B cell malignancies, please visit ClinicalTrials.gov.

On November 9, 2022 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported financial results for the third quarter ended September 30, 2022 and provided a corporate update (Press release, Celldex Therapeutics, NOV 9, 2022, View Source [SID1234623545]).

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"Celldex continued to execute towards our clinical and corporate milestones, making strong progress across multiple programs; importantly, this includes the initiation of our Phase 2 studies in chronic spontaneous and chronic inducible urticaria this past summer. As we near the close of 2022 and look to 2023, we anticipate a consistent stream of data readouts from the barzolvolimab program, starting in December with additional data from our Phase 1 study in chronic inducible urticaria," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "We are also enthusiastic about the potential of our bispecific platform and believe our strategic updates including the development of CDX-585, our ILT4 and PD-(L)1 bispecific antibody, which is expected to enter the clinic in 2023, will drive value for this platform."

"In summary, our recent advances of the barzolvolimab program, development of our bispecific platform, and strong balance sheet continue to position us very well to execute across our upcoming key clinical milestones. We look forward to continued momentum across the company for the rest of the year and providing updates in the coming months," concluded Mr. Marucci.

Recent Program Highlights

Barzolvolimab – KIT Inhibitor Program

Barzolvolimab is a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells.

In June and July 2022, Celldex announced that the first patients have been dosed in the Phase 2 clinical studies of barzolvolimab for the treatment of Chronic Spontaneous Urticaria (CSU) and the two most common forms of chronic inducible urticaria (CIndU) – cold urticaria (ColdU) and symptomatic dermographism (SD). These randomized, double-blind, placebo-controlled, parallel group Phase 2 studies are evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategies.

On June 30, Celldex reported interim data from the barzolvolimab multiple dose Phase 1b study in CSU which were presented as a late-breaking electronic poster presentation as part of the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress 2022. The Company has since completed enrollment to the 3 and 4.5 mg/kg dose groups and plans to present 12-week treatment data from these dose groups in February 2023.

EAACI 2022 Data Summary:

Barzolvolimab was well tolerated with a favorable safety profile; effects of multiple dose administration were consistent with observations in single dose studies. Barzolvolimab resulted in rapid, marked and durable responses in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment.
Mean reduction from baseline in urticaria activity (UAS7) of 66.6% in all patients in the 1.5 mg/kg dose group (n=8) at week 12 and 75.1% in all patients in the 3 mg/kg dose group (n=9) at week 8 (reflects only one dose), demonstrating clinically meaningful symptom improvements for patients.
Complete response (UAS7=0) of 57.1% in the 1.5 mg/kg dose group at week 12 and 44.4% at week 8 (reflects only one dose) in the 3 mg/kg dose group which is a key therapeutic goal.
75% well-controlled disease by Urticaria Control Test (UCT) in the 1.5 mg/kg dose group at week 12 and 83.3% in the 3 mg/kg dose group at week 8 (reflects only one dose).
Tryptase suppression paralleled symptom improvement, demonstrating the impact of mast cell depletion on CSU disease activity.

Celldex has completed enrollment in the barzolvolimab Phase 1b open label study in chronic inducible urticaria. The Company plans to present data from the 1.5 mg/kg cold urticaria cohort and long-term follow up from the 3 mg/kg symptomatic dermographism and cold urticaria cohorts in December. Patient follow up continues in the cholinergic cohort and is planned for presentation in mid-2023.

Celldex continues to enroll patients in the barzolvolimab Phase 1b multi-center, randomized, double-blind, placebo-controlled study in patients with prurigo nodularis (PN), a chronic skin disease characterized by the development of hard, intensely itchy (pruritic) nodules on the skin.

Celldex plans to initiate a Phase 2 international trial of barzolvolimab in eosinophilic esophagitis (EoE), the most common type of eosinophilic gastrointestinal disease, in the first half of 2023. The Company is finalizing clinical study design and completing the chronic toxicology study which will support study initiation in the United States.
Bispecific Antibody Platform

CDX-585 – Bispecific ILT4 & PD-(L)1

CDX-585 combines highly active PD-1 blockade with anti-ILT4 blockade to overcome immunosuppressive signals in T cells and myeloid cells. ILT4 is emerging as an important immune checkpoint on myeloid cells.

CDX-585 is currently completing CMC and IND-enabling activities and is expected to enter the clinic in 2023.
CDX-527 – Bispecific PD-L1 & CD27

CDX-527 utilizes the Company’s proprietary highly active anti-PD-L1 and CD27 human antibodies to couple CD27 co-stimulation with blockade of the PD-L1/PD-1 pathway.

The standard of care in ovarian cancer continues to evolve, making drug development in this indication more challenging. With multiple clinical trials actively recruiting in ovarian cancer, enrollment to the expansion cohort in patients with checkpoint naïve ovarian cancer (n=8) did not meet the Company’s internal timelines and a review of the results to date also did not meet internal hurdles for proceeding. Given the evolving environment and Celldex’s pipeline and resource priorities, the Company has decided to discontinue the program.
Third Quarter 2022 Financial Highlights and 2022 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2022 were $323.5 million compared to $356.8 million as of June 30, 2022. The decrease was primarily driven by third quarter cash used in operating activities of $35.2 million, which includes the $15.0 million payment to Shareholder Representative Services (SRS), the representative of the former stockholders of Kolltan Pharmaceuticals, Inc., pursuant to our settlement agreement. At September 30, 2022, Celldex had 47.1 million shares outstanding.

Revenues: Total revenue was $0.4 million in the third quarter of 2022 and $0.7 million for the nine months ended September 30, 2022, compared to $0.2 million and $4.3 million for the comparable periods in 2021. The decrease in revenue for the nine months ended September 30, 2022 compared to the nine months ended September 30, 2021 was primarily due to a decrease in services performed under our manufacturing and research and development agreements with Rockefeller University and Gilead Sciences.

R&D Expenses: Research and development (R&D) expenses were $21.6 million in the third quarter of 2022 and $59.4 million for the nine months ended September 30, 2022, compared to $13.6 million and $38.6 million for the comparable periods in 2021. The increase in R&D expenses was primarily due to an increase in barzolvolimab clinical trial, barzolvolimab contract manufacturing and personnel expenses.

G&A Expenses: General and administrative (G&A) expenses were $6.5 million in the third quarter of 2022 and $20.6 million for the nine months ended September 30, 2022, compared to $5.8 million and $14.2 million for the comparable periods in 2021. The increase in G&A expenses was primarily due to higher legal costs related to our settlement agreement with SRS, barzolvolimab commercial planning and stock-based compensation expenses.

Changes in Fair Value Remeasurement of Contingent Consideration: The Company recorded a $6.9 million gain on fair value remeasurement of contingent consideration for the nine months ended September 30, 2022, primarily due to the Company’s decision to deprioritize the CDX-1140 program in the second quarter of 2022.

Litigation Settlement Related Loss: The Company recorded a one-time loss of $15.0 million in the second quarter of 2022 related to the $15.0 million paid to SRS pursuant to our settlement agreement.

Net Loss: Net loss was $26.8 million, or ($0.57) per share, for the third quarter of 2022, and $85.8 million, or ($1.83) per share, for the nine months ended September 30, 2022, compared to a net loss of $20.5 million, or ($0.45) per share, for the third quarter of 2021 and $50.4 million, or ($1.21) per share, for the nine months ended September 30, 2021. The litigation settlement related loss had a ($0.32) impact on net loss per share for the nine months ended September 30, 2022. The gain on fair value remeasurement of contingent consideration had a $0.15 impact on net loss per share for the nine months ended September 30, 2022.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at September 30, 2022 are sufficient to meet estimated working capital requirements and fund planned operations through 2025.