Favorable safety profile in dose escalation shown to date; selective TEAD1 inhibition with IK-930 resulted in minimal treatment-related proteinuria without any dose reductions or treatment interruptions
Encouraging signs of clinical activity and tumor shrinkage in multiple patients with difficult-to-treat epithelioid hemangioendothelioma (EHE) during dose escalation
Additional IK-930 clinical data update planned for the second half of 2024; increased focus on enrollment of targeted populations including patients with mesothelioma and other NF2 mutant solid tumors
Pipeline build continues with clinical startup for IK-595, a MEK-RAF molecular glue, anticipated by end of 2023; Cash runway into 2026
“This early look at the IK-930 dose escalation data strongly supports our differentiated approach to targeting the Hippo pathway. Importantly, following the target biology and initially focusing on EHE has allowed us to observe clinical activity of IK-930 early in our dose escalation. Even in the projected efficacious exposure range and at doses with clinical activity, IK-930 has thus far circumvented the renal toxicity observed with pan-TEAD inhibitors,” commented
IK-930 Dose Escalation Summary and Emerging Proof of Concept in EHE
IK-930 selectively binds TEAD1 and broadly represses oncogenic TEAD signaling as a potent Hippo-pathway inhibitor, a known suppressor pathway in cancers such as epithelioid hemangioendothelioma (EHE), mesothelioma, meningioma, and others. IK-930’s differentiated paralog selectivity and robust repressor activity in complex with VGLL4 are key characteristics supporting anti-tumor effect in preclinical models. IK-930 is designed to circumvent renal toxicity, potentially resulting in an optimized therapeutic index. Twenty-six patients with a range of solid tumors were treated in the dose escalation portion of the study as of
Differentiated Safety Profile
- 26 patients have been treated with IK-930 in dose escalation as of
October 31, 2023 - IK-930 is in the final stages of dose optimization; the tolerability profile observed thus far supports the hypothesis that IK-930’s selectivity could provide a wider therapeutic index for this new class of compounds
- Proteinuria is an adverse effect of special interest as it may be an on-target effect of broad TEAD inhibition
- Treatment-related proteinuria was recorded in 3 out of 26 dose escalation patients and was limited to grade 1-2
- The observed proteinuria did not result in dose reduction or treatment interruption; no proteinuria events were considered dose-limiting and in all cases was fully reversible
- Other safety observations include:
- Frequent adverse events to date have been low-grade nausea, fatigue, and diarrhea, and have not required any dose reduction
- Two EHE patients with significant liver metastases experienced reversible liver enzyme elevation
- One of these patients developed treatment-related grade 3 elevation, deemed dose limiting (the only DLT observed), and the patient remains on study after dose adjustment
- The other patient experienced grade 3-4 elevation that was deemed possibly treatment related;
- Dose escalation is currently ongoing
- 15 patients were treated with doses within the projected efficacious exposure range and pharmacokinetic data showed some variability
- 7 out of 15 patients were determined to reach efficacious exposure
- Target engagement in tumor, as determined by decreased TEAD gene signature, has been demonstrated in the efficacious dose range
- To minimize IK-930 exposure variability, a next generation formulation is now being evaluated in the dose escalation
- Recommended dosing for the next stage of the IK-930 program is expected to be determined in the near-term
Emerging Proof of Concept in EHE
Epithelioid hemangioendothelioma is a rare vascular sarcoma defined by gene fusions of either YAP or TAZ genes in the Hippo pathway with other transcriptional regulators. EHE is a slow-growing, invasive tumor with no approved treatment options and is challenging to measure due to diffuse infiltration of multiple organs. It can occur in multiple areas of the body, including the liver, lungs, bones, and blood vessels. People with EHE suffer symptoms that relentlessly affect their quality of life and are consistent with the site of the EHE growth, including liver failure, respiratory issues, and gastrointestinal symptoms, which are frequently accompanied by severe pain across the body. With no approved standard of care, there is substantial need for innovative treatments that can provide clinical benefit and symptom relief and slow or limit the progression of disease.
- Seven patients with EHE have been treated with IK-930 in the dose escalation portion of the trial
- 7 out of 7 EHE patients reached stable disease as a best response so far as measured by RECIST
- 3 out of the 7 patients experienced tumor shrinkage in multiple target and non-target lesions
- 4 out of 7 highly symptomatic EHE patients enrolled across multiple dose levels reported symptomatic improvement and subjective improvement of quality of life such as improved energy, weight gain, and pain control
- 3 out of the 7 patients continue on treatment with time on treatment ranging from 18 to 26 weeks and ongoing
- As a result of these initial tolerability and antitumor activity findings, enrollment in the dose escalation phase continues to progress in targeted populations including mesothelioma and meningioma, in addition to EHE
- Based on preclinical data indicating IK-930 synergy with EGFR inhibitors to combat therapeutic resistance, a combination cohort for IK-930 and osimertinib in patients with EGFR-mutant non-small cell lung cancer (NSCLC) is planned to initiate in 2024
- An additional data update from the IK-930 clinical program is planned for the second half of 2024
“EHE is a rare soft tissue sarcoma for which there is no known treatment. This tumor is 100% driven by the Hippo pathway which has motivated our initial development of IK-930 in EHE, despite the challenge of assessing the disease burden and treatment effects. The EHE patient community is one of the strongest I have worked with. The physicians, patients, and supportive community are deeply committed to finding innovative solutions in EHE, and we are immensely grateful for their partnership in these early days of the IK-930 clinical program,” commented
“The EHE community is excited by this early data from IK-930, the first targeted agent for patients with EHE, and we eagerly await more data. Rare cancers, like EHE, present significant challenges for drug developers, and we are encouraged by Ikena’s commitment to this program. We are grateful for the participation of EHE patients, caregivers, and physicians in the trial, and we look forward to continuing our partnership with Ikena,” commented
Summary of Additional Recent Pipeline Progress and Corporate Updates
IK-595: MEK-RAF Molecular Glue
- IK-595 clinical trial anticipated to initiate by year end 2023
- Additional preclinical updates were presented at the 5th Annual
RAS-Targeted Drug Development Conference inSeptember and AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in October
IK-175: AHR Inhibitor in Collaboration with
- The Phase 1 clinical trial in urothelial carcinoma has completed enrollment and the program is eligible for opt-in from
Bristol Myers Squibb through early 2024
Corporate Updates
- In
August 2023 , the Company acquiredPionyr Immunotherapeutics, Inc. (“Pionyr”), a privately held biotech company, in an all-stock transaction- Ikena acquired all of Pionyr assets, including approximately
$43 million in net cash in exchange for shares of Ikena stock at price of$7.15 per share - The valuation for the transaction was determined solely by net cash available at closing
- Ikena acquired all of Pionyr assets, including approximately
- The Company believes that cash at hand will be sufficient to meet its operating requirements into 2026 through multiple data events for both IK-930 and IK-595
Financial Results for the Quarter Ended
As of
Collaboration revenue was
Research and development expenses were
General and administrative expenses were
About
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding: the timing and advancement of our targeted oncology programs, including the timing of updates; our expectations regarding the therapeutic benefit of our targeted oncology programs; our ability to efficiently discover and develop product candidates; our ability to obtain and maintain regulatory approval of our product candidates; expectations with respect to projected cash runway; the anticipated use of proceeds from the Pionyr acquisition; the implementation of our business model; and strategic plans for our business and product candidates. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the timing and advancement of our targeted oncology programs; our expectations regarding the therapeutic benefit of our targeted oncology programs; our ability to efficiently discover and develop product candidates; the implementation of our business model, and strategic plans for our business and product candidates, the sufficiency of the Company’s capital resources to fund operating expenses and capital expenditure requirements and the period in which such resources are expected to be available, and other factors discussed in the “Risk Factors” section of Ikena’s Quarterly Report on Form 10-Q for the quarter ended
Investor Contact:
rcohen@ikenaoncology.com
Media Contact:
lshiplo@lifescicomms.com
Selected Balance Sheet Items: | 2023 | 2022 | ||||||
Cash and cash equivalents | $ | 121,277 | $ | 59,919 | ||||
Marketable securities | $ | 75,656 | $ | 97,028 | ||||
Total assets | $ | 215,335 | $ | 172,259 | ||||
Total liabilities | $ | 28,146 | $ | 25,290 | ||||
Convertible Preferred Stock | $ | 31,845 | $ | - | ||||
Additional paid-in-capital | $ | 418,486 | $ | 361,915 | ||||
Accumulated deficit | $ | (262,896 | ) | $ | (214,219 | ) | ||
Total stockholders' equity | $ | 155,344 | $ | 146,969 |
Selected Financial Information | ||||||||||||||||
(in thousands, except share and per share data) | ||||||||||||||||
Statement of Operations Items: | Three Months Ended | Nine Months Ended | ||||||||||||||
2023 | 2022 | 2023 | 2022 | |||||||||||||
Research and development revenue under collaboration agreement | $ | 1,185 | $ | 6,402 | $ | 8,501 | $ | 10,168 | ||||||||
Operating expenses: | ||||||||||||||||
Research and development | 14,654 | 18,850 | 45,378 | 48,682 | ||||||||||||
General and administrative | 6,034 | 5,428 | 16,632 | 17,276 | ||||||||||||
Total operating expenses | 20,688 | 24,278 | 62,010 | 65,958 | ||||||||||||
Loss from operations | (19,503 | ) | (17,876 | ) | (53,509 | ) | (55,790 | ) | ||||||||
Investment income | 2,162 | 550 | 4,840 | 1,135 | ||||||||||||
Other expense | (2 | ) | (12 | ) | (8 | ) | (13 | ) | ||||||||
Total other income, net | 2,160 | 538 | 4,832 | 1,122 | ||||||||||||
Net loss | $ | (17,343 | ) | $ | (17,338 | ) | $ | (48,677 | ) | $ | (54,668 | ) | ||||
Other comprehensive loss: | ||||||||||||||||
Unrealized gain (loss) on marketable securities | 166 | (77 | ) | (290 | ) | (1,181 | ) | |||||||||
Total comprehensive loss | $ | (17,177 | ) | $ | (17,415 | ) | $ | (48,967 | ) | $ | (55,849 | ) | ||||
Net loss per share: | ||||||||||||||||
Net loss per share attributable to common stockholders basic and diluted | $ | (0.40 | ) | $ | (0.48 | ) | $ | (1.23 | ) | $ | (1.51 | ) | ||||
Weighted-average common stocks outstanding, basic and diluted | 43,437,844 | 36,257,074 | 39,688,984 | 36,165,143 | ||||||||||||
Source:
2023 GlobeNewswire, Inc., source