Kezar Life Sciences Announces Positive Topline Results from the PORTOLA Phase 2a Trial Evaluating Zetomipzomib for the Treatment of Patients with Autoimmune Hepatitis (AIH) and Reports Fourth Quarter and Year End 2024 Financial Results
Kezar Life Sciences (KZR) announced positive topline results from the PORTOLA Phase 2a trial evaluating zetomipzomib for autoimmune hepatitis (AIH) treatment. In the trial's key findings, 36% of zetomipzomib-treated patients achieved complete biochemical response with significant steroid reduction, compared to 0% in the placebo group.
The study demonstrated that in the intention-to-treat population, 31% of zetomipzomib patients achieved complete response and steroid taper, versus one placebo patient. Notably, the median response duration was 27.6 weeks, with no disease flares reported in responding patients.
Financial highlights as of December 31, 2024:
- Cash position: $132.2 million
- R&D expenses decreased to $65.7 million from $85.7 million in 2023
- G&A expenses reduced to $23.4 million from $26.5 million in 2023
- Net loss: $83.7 million ($11.49 per share)
Kezar Life Sciences (KZR) ha annunciato risultati positivi preliminari dal trial PORTOLA di fase 2a che valuta il zetomipzomib per il trattamento dell'epatite autoimmune (AIH). Tra i principali risultati dello studio, il 36% dei pazienti trattati con zetomipzomib ha raggiunto una risposta biochimica completa con una significativa riduzione degli steroidi, rispetto allo 0% nel gruppo placebo.
Lo studio ha dimostrato che nella popolazione intention-to-treat, il 31% dei pazienti trattati con zetomipzomib ha ottenuto una risposta completa e una riduzione degli steroidi, contro un paziente nel gruppo placebo. È importante notare che la durata mediana della risposta è stata di 27,6 settimane, senza segnalazioni di riacutizzazioni della malattia nei pazienti rispondenti.
Risultati finanziari al 31 dicembre 2024:
- Posizione di cassa: 132,2 milioni di dollari
- Spese per R&S diminuite a 65,7 milioni di dollari rispetto a 85,7 milioni di dollari nel 2023
- Spese generali e amministrative ridotte a 23,4 milioni di dollari rispetto a 26,5 milioni di dollari nel 2023
- Perdita netta: 83,7 milioni di dollari (11,49 dollari per azione)
Kezar Life Sciences (KZR) anunció resultados preliminares positivos del ensayo PORTOLA de fase 2a que evalúa el zetomipzomib para el tratamiento de la hepatitis autoinmune (AIH). En los hallazgos clave del ensayo, el 36% de los pacientes tratados con zetomipzomib lograron una respuesta bioquímica completa con una reducción significativa de esteroides, en comparación con el 0% en el grupo placebo.
El estudio demostró que en la población por intención de tratar, el 31% de los pacientes con zetomipzomib lograron una respuesta completa y una reducción de esteroides, frente a un paciente en el grupo placebo. Cabe destacar que la duración media de la respuesta fue de 27.6 semanas, sin informes de brotes de la enfermedad en los pacientes que respondieron.
Aspectos financieros al 31 de diciembre de 2024:
- Posición de efectivo: 132.2 millones de dólares
- Gastos en I+D disminuyeron a 65.7 millones de dólares desde 85.7 millones de dólares en 2023
- Gastos generales y administrativos reducidos a 23.4 millones de dólares desde 26.5 millones de dólares en 2023
- Pérdida neta: 83.7 millones de dólares (11.49 dólares por acción)
Kezar Life Sciences (KZR)는 자가면역 간염(AIH) 치료를 위한 zetomipzomib의 PORTOLA 2a 단계 시험에서 긍정적인 주요 결과를 발표했습니다. 시험의 주요 결과에서, zetomipzomib 치료를 받은 환자의 36%가 상당한 스테로이드 감소와 함께 완전한 생화학적 반응을 달성했으며, 이는 위약 그룹의 0%에 비해 높은 수치입니다.
이 연구는 치료 의도 인구에서 zetomipzomib 환자의 31%가 완전한 반응과 스테로이드 감소를 달성했으며, 위약 그룹에서는 단 한 명의 환자만이 이에 해당한다고 보여줍니다. 특히, 반응 지속 기간의 중앙값은 27.6주였으며, 반응한 환자에서 질병 악화는 보고되지 않았습니다.
2024년 12월 31일 기준 재무 하이라이트:
- 현금 보유: 1억 3220만 달러
- R&D 비용은 6570만 달러로 2023년의 8570만 달러에서 감소
- G&A 비용은 2340만 달러로 2023년의 2650만 달러에서 감소
- 순손실: 8370만 달러 (주당 11.49 달러)
Kezar Life Sciences (KZR) a annoncé des résultats préliminaires positifs de l'essai PORTOLA de phase 2a évaluant le zetomipzomib pour le traitement de l'hépatite auto-immune (AIH). Parmi les principales conclusions de l'essai, 36 % des patients traités par zetomipzomib ont atteint une réponse biochimique complète avec une réduction significative des stéroïdes, contre 0 % dans le groupe placebo.
L'étude a démontré que dans la population intention de traiter, 31 % des patients recevant du zetomipzomib ont atteint une réponse complète et une réduction des stéroïdes, contre un patient dans le groupe placebo. Il est à noter que la durée médiane de la réponse était de 27,6 semaines, sans signalement de poussées de la maladie chez les patients répondants.
Points financiers au 31 décembre 2024 :
- Position de trésorerie : 132,2 millions de dollars
- Les dépenses de R&D ont diminué à 65,7 millions de dollars contre 85,7 millions de dollars en 2023
- Les frais généraux et administratifs ont été réduits à 23,4 millions de dollars contre 26,5 millions de dollars en 2023
- Perte nette : 83,7 millions de dollars (11,49 dollars par action)
Kezar Life Sciences (KZR) gab positive vorläufige Ergebnisse aus der PORTOLA-Phase-2a-Studie bekannt, die zetomipzomib zur Behandlung von Autoimmunhepatitis (AIH) bewertet. In den wichtigsten Ergebnissen der Studie erreichten 36 % der mit zetomipzomib behandelten Patienten eine vollständige biochemische Reaktion mit einer signifikanten Reduzierung von Steroiden, verglichen mit 0 % in der Placebo-Gruppe.
Die Studie zeigte, dass in der Intention-to-Treat-Population 31 % der zetomipzomib-Patienten eine vollständige Reaktion und Steroidreduktion erreichten, im Vergleich zu einem Patienten in der Placebo-Gruppe. Bemerkenswert ist, dass die mediane Reaktionsdauer 27,6 Wochen betrug, ohne dass bei den ansprechenden Patienten Krankheitsschübe berichtet wurden.
Finanzielle Höhepunkte zum 31. Dezember 2024:
- Liquiditätsposition: 132,2 Millionen US-Dollar
- F&E-Ausgaben sanken auf 65,7 Millionen US-Dollar von 85,7 Millionen US-Dollar im Jahr 2023
- Allgemeine und Verwaltungskosten wurden auf 23,4 Millionen US-Dollar von 26,5 Millionen US-Dollar im Jahr 2023 gesenkt
- Nettoverlust: 83,7 Millionen US-Dollar (11,49 US-Dollar pro Aktie)
- Positive efficacy data with 36% complete response rate in zetomipzomib-treated patients vs 0% placebo
- Strong durability of response with 27.6-week median duration and no disease flares
- Favorable safety profile in 6-month treatment period
- Substantial cash position of $132.2 million
- Reduced operating expenses with R&D costs down by $20 million year-over-year
- Net loss of $83.7 million in 2024
- Revenue decreased by $7.0 million compared to 2023
- Cash position declined from $201.4 million in 2023 to $132.2 million in 2024
- Partial clinical hold by FDA needs to be removed before proceeding
Insights
Kezar Life Sciences has delivered encouraging Phase 2a results for zetomipzomib in autoimmune hepatitis (AIH), representing the first successful randomized study in treatment-refractory AIH patients. The drug demonstrated meaningful clinical benefits in steroid-sparing biochemical remissions - a critical endpoint for AIH therapy where steroid dependency remains a significant clinical challenge.
The most compelling data point comes from the pre-specified steroid-dependent subgroup, where 35.7% of zetomipzomib patients achieved complete biochemical response with steroid reduction to ≤5 mg/day versus 0% in the placebo arm. This steroid-sparing effect addresses a substantial unmet need, as chronic steroid use carries significant morbidity.
The durability of response (median 27.6 weeks) without disease flares among responders further strengthens the clinical profile. While the trial wasn't powered for efficacy, these signals in a difficult-to-treat population provide a solid foundation for designing a potential registrational study.
The safety profile appears manageable with injection site reactions being most common. The company's
Kezar's financial position shows disciplined capital management while advancing its clinical programs. The
Annual operating expenses decreased meaningfully, with R&D expenses down
The net loss narrowed to
With positive Phase 2a data now in hand, Kezar will need to allocate resources toward the pivotal program while maintaining financial discipline. The company's market capitalization of
Company-hosted conference call and webcast to be held today at 8:00 a.m. ET
- Zetomipzomib treatment results in steroid-sparing biochemical remissions in accordance with AASLD treatment guidelines in a difficult-to-treat, refractory AIH patient population.
-
In relapsed, steroid-dependent AIH patients, of the 21 of 24 entering screening on steroid-based therapy,
36% (5 of 14) of zetomipzomib-treated patients achieved a complete biochemical response (CR) and clinically significant steroid taper to 5 mg/day or less, compared to 0 of 7 of placebo patients. -
In the intention-to-treat (ITT) population,
31% (5 of 16) of zetomipzomib patients achieved a CR and steroid taper (≤5 mg/day), compared to 1 of 8 placebo patients. - Median duration of response in zetomipzomib patients achieving a CR was 27.6 weeks (including the ongoing open-label extension), and no disease flares were reported in any zetomipzomib-treated patient achieving CR during study.
- Favorable safety profile was observed during the 6-month, blinded treatment period.
-
Cash, cash equivalents and marketable securities totaled
as of December 31, 2024$132 million
“We are pleased to announce these exciting results from the
“I am impressed by the totality of efficacy and safety data from the
The primary efficacy endpoint of
Summary of Topline Results
-
Without regard to steroid taper,
50.0% (8 of 16) of zetomipzomib patients achieved a CR, compared to37.5% (3 of 8) of placebo patients. -
31.3% (5 of 16) of zetomipzomib patients achieved both a CR and steroid taper to 5 mg/day or less, compared to12.5% (1 of 8) of placebo patients. -
18.8% (3 of 16) of zetomipzomib patients achieved both a CR and complete steroid withdrawal to zero mg/day, compared to0% (0 of 8) of placebo patients. -
Median duration of response in zetomipzomib patients achieving a CR was 27.6 weeks (including the ongoing open-label extension), and no disease flares were reported in any zetomipzomib-treated patient achieving CR. Disease flares were defined as a sustained increase in ALT values to
25% above the CR value or 1.25-fold higher than the upper limit of normal for more than one week and requiring a restart or increase in steroid dose.
In the pre-specified subgroup analysis, 21 of the 24 patients entered the study on a steroid-based therapy at the time of screening. One patient in the placebo arm and two patients in the zetomipzomib arm were not receiving steroids at screening. All patients on study were required to initiate treatment with an initial prednisone dose of 20–40 mg/day. Of the 21 patients in this subgroup analysis:
- Median steroid use at screening was 20 mg/day for patients enrolled in the zetomipzomib arm, compared to 10 mg/day in the placebo arm, indicating that the zetomipzomib-treated arm was more refractory than the placebo arm.
-
Without regard to steroid taper,
57.1% (8 of 14) of zetomipzomib patients achieved a CR, compared to28.6% (2 of 7) of placebo patients. -
35.7% (5 of 14) of patients on the zetomipzomib arm achieved a CR and steroid taper to 5 mg/day or less, compared to0% (0 of 7) of placebo patients. -
21.4% (3 of 14) of patients on the zetomipzomib arm achieved a CR and complete steroid withdrawal to zero mg/day, compared to0% (0 of 7) of placebo patients.
Safety
Treatment-emergent adverse events (TEAEs) were seen in all patients, with injection site reactions (ISRs) being the most commonly reported TEAE in both arms. Systemic injection reactions (SIRs), with onset occurring 8 to 24 hours post-dose and usually resolving within 48 hours, were all Grade 1 and Grade 2. SIRs are a protocol-defined set of specific adverse events (AEs) consisting of one or more of the following signs/symptoms: hypotension, tachycardia, nausea, vomiting, dizziness, headache, pyrexia, rigors and/or chills.
Three patients experienced treatment-emergent serious adverse events (SAEs): one in the placebo arm, a Grade 3 variceal bleeding with hematemesis and atrial fibrillation; and two in the zetomipzomib arm, a Grade 3 fever occurring after the Week 24 liver biopsy, and a Grade 3 influenza infection that fully resolved during study. All SAEs were considered unrelated to study treatment, and all three patients completed the double-blind treatment period. Infectious AEs were reported in
|
Placebo |
Zetomipzomib |
|
n=7 |
n=16 |
Adverse Events in Double-blind Treatment Period |
n (%) |
n (%) |
Participants with at least 1 Treatment Emergent Adverse Event (TEAE) |
7 (100.0) |
16 (100.0) |
Most common TEAE: |
|
|
Injection Site Reaction (ISR) |
4 (57.1) |
15 (93.8) |
Systemic Injection Reaction (SIR) |
1 (14.3) |
12 (75.0) |
TEAE leading to study drug discontinuation |
0 (0) |
3 (18.8) |
Grade 3 TEAE (no Grade 4 or 5 TEAEs reported) |
1 (14.3) |
3 (18.8) |
Serious TEAE |
1 (14.3) |
2 (12.5) |
Infectious TEAE |
6 (85.7) |
9 (56.3) |
Grade ≥3 Infectious TEAE |
0 (0) |
1 (6.3) |
Opportunistic Infections |
0 (0) |
0 (0) |
Death |
0 (0) |
0 (0) |
Financial Results
-
Cash, cash equivalents and marketable securities totaled
as of December 31, 2024, compared to$132.2 million as of December 31, 2023. The decrease was primarily attributable to cash used in operations to advance clinical-stage programs.$201.4 million -
Revenue decreased by
in 2024 compared to 2023 due to the October 2023 upfront payment received under the collaboration and license agreement with Everest Medicines.$7.0 million -
Research and development (R&D) expenses for the fourth quarter of 2024 decreased by
to$6.6 million , compared to$16.0 million in the fourth quarter of 2023. Full year R&D expenses decreased by$22.6 million to$20.0 million in 2024, compared to$65.7 million in 2023. This decrease was primarily due to the Company’s strategic restructuring in October 2023 to prioritize its clinical-stage programs, reducing personnel-related costs and spending in its early-stage research activities, and a$85.7 million milestone payment made in 2023 under Kezar’s exclusive license agreement with Onyx Therapeutics. The decrease was partially offset by the increased clinical trial costs related to the PALIZADE and$5.0 million PORTOLA trials. -
General and administrative (G&A) expenses for the fourth quarter of 2024 decreased by
to$0.3 million compared to$5.5 million in the fourth quarter of 2023. Full year G&A expenses decreased by$5.8 million to$3.1 million in 2024, compared to$23.4 million in 2023. The decrease was primarily due to a decrease in legal and professional service expenses and non-cash stock-based compensation.$26.5 million -
Restructuring and impairment charges decreased by
to$4.7 million in 2024, compared to$1.5 million in 2023. The decrease was primarily related to one-time severance-related costs made in 2023 and higher impairment costs recognized in 2023 than 2024 on the right-of-use asset for the vacated floor in the leased office facility and certain equipment no longer utilized.$6.2 million -
Net loss for the fourth quarter of 2024 was
, or$20.2 million per basic and diluted common share, compared to a net loss of$2.77 , or$32.3 million per basic and diluted common share, for the fourth quarter of 2023. Net loss for 2024 was$4.44 , or$83.7 million per basic and diluted common share, compared to a net loss of$11.49 , or$101.9 million per basic and diluted common share in 2023. The weighted-average shares used to compute net loss per basic and diluted common share have been retroactively adjusted to reflect the one-for-ten reverse stock split completed on October 29, 2024.$14.04 - Total shares of common stock outstanding was 7.3 million shares as of December 31, 2024, after taking into effect the one-for-ten reverse stock split completed on October 29, 2024.
Conference Call and Webcast
Kezar Life Sciences will host a webcast and conference call today, March 25, 2025, at 8:00 a.m. ET to discuss topline results from the
A live webcast of the event can also be found on the Kezar website at https://ir.kezarlifesciences.com/news-events/events-presentations. A replay of the event will be available for 90 days following the presentation.
About Zetomipzomib
Zetomipzomib is a novel, first-in-class, selective immunoproteasome inhibitor with broad therapeutic potential across multiple autoimmune diseases. Preclinical research demonstrates that selective immunoproteasome inhibition results in a broad anti-inflammatory response in animal models of several autoimmune diseases, while avoiding immunosuppression. Data generated from completed clinical trials provide evidence that zetomipzomib exhibits a favorable safety and tolerability profile for development in severe, chronic autoimmune diseases.
About Autoimmune Hepatitis
Autoimmune hepatitis (AIH) is a rare chronic disease in which the immune system attacks the liver and causes inflammation and tissue damage, severely impacting patients’ physical health and quality of life. Lifelong maintenance therapy is required to avoid relapse and burdensome adverse effects. If left untreated, AIH can lead to cirrhosis, liver failure and hepatocellular carcinoma. In
About Kezar Life Sciences
Kezar Life Sciences is a clinical-stage biopharmaceutical company developing novel small molecule therapeutics to treat unmet needs in immune-mediated diseases. Zetomipzomib, a selective immunoproteasome inhibitor, is currently being evaluated in a Phase 2a clinical trial for autoimmune hepatitis. This product candidate also has the potential to address multiple chronic immune-mediated diseases. For more information, visit www.kezarlifesciences.com, and follow us on LinkedIn, Facebook, Twitter and Instagram.
Cautionary Note on Forward-looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “can,” “should,” “expect,” “believe,” “potential,” “anticipate” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Kezar’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause Kezar’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the design, initiation, progress, timing, scope and results of ongoing and potential future clinical trials, preliminary nature of topline data from our clinical trials, the likelihood that data will support future development and therapeutic potential, the association of data with treatment outcomes, expectations regarding the removal of the partial clinical hold in the
KEZAR LIFE SCIENCES, INC. |
||||||||
Selected Balance Sheets Data |
||||||||
(In thousands) |
||||||||
|
|
|
||||||
December 31, 2024 |
|
December 31, 2023 |
||||||
Cash, cash equivalents and marketable securities |
$ |
132,245 |
|
$ |
201,372 |
|
||
Total assets |
|
144,682 |
|
|
221,235 |
|
||
Total current liabilities |
|
20,329 |
|
|
17,744 |
|
||
Total noncurrent liabilities |
|
7,437 |
|
|
15,921 |
|
||
Total stockholders' equity |
|
116,916 |
|
|
187,570 |
|
||
Summary of Operations Data |
||||||||||||||||
(In thousands except share and per share data) |
||||||||||||||||
Three Months Ended |
|
Year Ended |
||||||||||||||
December 31 |
|
December 31 |
||||||||||||||
2024 |
|
2023 |
|
2024 |
|
2023 |
||||||||||
Collaboration revenue |
$ |
- |
|
$ |
- |
|
$ |
- |
|
$ |
7,000 |
|
||||
Operating expenses: |
||||||||||||||||
Research and development |
|
16,030 |
|
|
22,643 |
|
|
65,742 |
|
|
85,697 |
|
||||
General and administrative |
|
5,545 |
|
|
5,759 |
|
|
23,393 |
|
|
26,540 |
|
||||
Impairment charge |
|
(12 |
) |
|
6,187 |
|
|
1,470 |
|
|
6,187 |
|
||||
Total operating expenses |
|
21,563 |
|
|
34,589 |
|
|
90,605 |
|
|
118,424 |
|
||||
Loss from operations |
|
(21,563 |
) |
|
(34,589 |
) |
|
(90,605 |
) |
|
(111,424 |
) |
||||
Interest income |
|
1,734 |
|
|
2,728 |
|
|
8,462 |
|
|
11,104 |
|
||||
Interest expense |
|
(389 |
) |
|
(399 |
) |
|
(1,593 |
) |
|
(1,550 |
) |
||||
Net loss |
$ |
(20,218 |
) |
$ |
(32,260 |
) |
$ |
(83,736 |
) |
$ |
(101,870 |
) |
||||
Net loss per common share, basic and diluted |
$ |
(2.77 |
) |
$ |
(4.44 |
) |
$ |
(11.49 |
) |
$ |
(14.04 |
) |
||||
Weighted-average shares used to compute net loss per common share, basic and diluted (1) |
|
7,300,007 |
|
|
7,273,696 |
|
|
7,290,245 |
|
|
7,255,365 |
|
(1) |
Shares outstanding have been retroactively adjusted to reflect the one-for-ten reverse stock split completed on October 29, 2024. |
View source version on businesswire.com: https://www.businesswire.com/news/home/20250325918238/en/
Investor and Media Contact:
Gitanjali Jain
Senior Vice President, Investor Relations and External Affairs
Kezar Life Sciences, Inc.
gjain@kezarbio.com
Source: Kezar Life Sciences, Inc.