UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN ISSUER
PURSUANT TO RULE 13a-16 OR 15d-16
OF THE SECURITIES EXCHANGE ACT OF 1934
For the month of August 2023
(Commission File No. 001-40241)
LAVA Therapeutics N.V.
(Translation of registrant’s name into English)
Yalelaan 62
3584 CM Utrecht, The Netherlands
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F ☒ Form 40-F ☐
LAVA Therapeutics, N.V.
EXHIBIT LIST
Exhibit |
| Description |
99.01 | | |
| | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| LAVA Therapeutics, N.V. | |
| (Registrant) | |
| | |
Date: August 15, 2023 | By: | /s/ Fred Powell |
| Fred Powell | |
| Chief Financial Officer |
Gamma-delta T cell engagers for the development of next-generation cancer therapeutics Corporate Presentation August 2023 |
Legal Disclosure: Forward-looking Statements 2 This presentation contains statements that constitute forward-looking statements. Many of the forward-looking statements contained in this presentation can be identified by the use of forward-looking words such as “anticipate,” “believe,” “could,” “expect,” “should,” “plan,” “intend,” “estimate” and “potential,” and similar terms and phrases. Forward-looking statements appear in a number of places in this presentation and include, but are not limited to, statements regarding our intent, belief or current expectations. Forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to our management. Such statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various important factors. These risk and uncertainties include, among other things, the potential use of our product candidates to treat various tumor targets; the timing and results of our research and development programs, preclinical studies and clinical trials, including the availability of data therefrom, expectations regarding enrollment in clinical trials, the timing of our clinical trial for LAVA-1207, and the submission of INDs or CTAs for our other product candidates; the expected safety profile of LAVA’s product candidates; our ability to develop and obtain regulatory approval for and commercialize any of our product candidates; the ability of low-dose interleukin-2 to increase the number of V9V2 T cells available for engagement by LAVA’s product candidates; the ability of LAVA’s collaborators to support or advance collaborations or our product candidates; any payments to us under our license agreement with Seagen or our agreements with our collaborators and our cash runway; our ability to leverage our initial programs to develop additional product candidates using our Gammabody® platform; and the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials. In addition, there may be adverse effects on our business condition and results from general economic and market conditions and overall fluctuations in the United States and international equity markets, including deteriorating market conditions due to investor concerns regarding inflation and hostilities between Russia and Ukraine, and recent and potential future disruptions in access to bank deposits or lending commitments due to bank failures. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward‐looking statements, see the "Risk Factors" section, as well as discussions of potential risks, uncertainties and other important factors, in the filings we make with the Securities and Exchange Commission from time to time. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. Although we believe that we have a reasonable basis for each forward-looking statement contained in this presentation, the events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. We qualify all of our forward-looking statements by these cautionary statements. Any forward-looking statements represent the Company’s views only as of the date of this presentation and do not represent its views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements. By attending this presentation, you acknowledge and agree that you are cautioned not to place undue reliance on any forward-looking statements, and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of the Company. |
Pioneering Next-Generation Cancer Therapeutics ©LAVA Therapeutics 2023 3 • Bispecific antibody platform to engage V9V2 T cells for highly specific tumor cell killing – Leverage the unique quality of V9V2 T cells to selectively kill tumor cells – Gammabody® combines potent tumor cell killing with no activation of suppressive regulatory T cells, low potential for on-target/off-tumor toxicity and cytokine release syndrome Proprietary Gammabody® platform • LAVA-1207 (PSMA) Phase 1/2a trial for mCRPC enrolling. Most recent data released at ASCO GU Feb 2023 − Favorable safety profile to date, preliminary signs of anti-tumor activity were observed • LAVA-051 (CD1d) Phase 1a no longer recruiting and will be discontinued after no patients remain on treatment − Trial showed favorable safety profile and initial anti-tumor activity in patients with relapsed and refractory chronic lymphocytic leukemia and multiple myeloma Clinical stage company • Seagen: licensed SGN-EGFRd2 (LAVA-1223) IND cleared • Janssen: licensed undisclosed Gammabody® candidate; Onboarded June 2023 • LAVA-1266 (CD123) IND/CTA enabling activities ongoing, expected to be ready 1H 2024 • Multiple preclinical programs Robust pipeline • $112.4M (Q2 2023) in cash, cash equivalents and investments; cash runway into 2026 Solid financials |
MM: multiple myeloma CLL: chronic lymphocytic leukemia AML: acute myeloid leukemia PSMA: prostate-specific membrane antigen EGFR: epidermal growth factor receptor mCRPC: metastatic castration-resistant prostate cancer Gammabody® Pipeline: Potential in Hematological and Solid Tumor Indications 4 ©LAVA Therapeutics 2023 Candidate Target Indication(s) Discovery Preclinical Phase 1 Phase 2 Anticipated Milestones & Recent Updates LAVA-1207 PSMA mCRPC • Most recent data released: ASCO GU 1Q 2023 • Next data release expected within 12 months LAVA-051 CD1d MM CLL AML • Enrollment has been discontinued • Complete Phase 1 clinical trial data to be presented when final patients end treatment SGN-EGFRd2 (LAVA-1223) EGFR Solid Tumors • Licensed to Seagen 3Q 2022 • IND cleared • Phase 1 Study in Advanced Solid Tumors expected to begin 2023 Janssen Collaboration undisclosed • Lead candidate selected by Janssen 2Q 2023 LAVA-1266 CD123 Hematologic Malignancies • IND/CTA enabling activities ongoing, expected to be ready 1H 2024 LAVA-1278 CD40 Hematologic Malignancies Hematologic malignancy Discontinued Solid Tumor Undisclosed |
Ton Adang, PhD CDO • Vast experience in drug development • Extensive experience in product discovery and project management (e.g., KEYTRUDA) HansvanderVliet,MD,PhD CSO • Inventor of LAVA’s gamma-delta T cell engager platform • Medical oncologist, extensive experience in preclinical and clinical research Team Led by Experienced Leaders in the Biotech and Pharma Field • Extensive global, diversified legal and team building experience • Almost 20 years practicing law, including over 15 years in the biotech and pharmaceutical industry Amy Garabedian, MSc, JD General Counsel Steve Hurly, MSc, MBA President & CEO • 25+ years leadership experience in life sciences industry • Seasoned drug developer and biotech strategist • 20+ years of global CFO/leadership experience in biopharma • Deep expertise across investor relations, finance, capital markets, operations and information technology Fred Powell CFO ©LAVA Therapeutics 2023 5 Charles Morris, MBChB, MRCP CMO • Medical oncologist, seasoned CMO with 25+ years of global oncology drug development • Supported several approvals including including TREANDA® (bendamustine and Faslodex® (fulvestrant) Robin Hume SVP, Head of Regulatory Affairs • 20+ years in global biopharmaceutical product and regulatory strategy experience • Proven track record in early and late-stage drug development, approval, launch and commercialization |
LAVA’s Proprietary Gammabody® Platform Bispecific Gamma-Delta T Cell Engagers |
glofitamab (DLBCL) Approved in the US in 2023 Source: The Antibody Society Data as of May 31, 2023 ©LAVA Therapeutics 2023 7 • High expectations for T cell bispecific therapies driving significant development • 200+ bispecific antibodies in the clinic, 6 bsTCEs currently approved Enthusiasm for Bispecific T Cell Engagers 1 0 1 0 3 1 0 0 0 1 6 4 5 5 10 16 17 21 35 45 31 65 59 0 10 20 30 40 50 60 70 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 blinatumomab (B cell leukemia) Approved in the US in 2014 Approved in the EU in 2015 BiTE Triomab tebentafusp (uveal melanoma) Approved in the US in 2022 Approved in the EU in 2022 Number of bispecific antibodies Year bispecific antibody first entered the clinic mosunetuzumab (lymphoma) Approved in the US in 2022 Approved in the EU in 2022 Common LC bsAb DuoBody teclistamab (multiple myeloma) Approved in the US in 2022 Approved in the EU in 2022 Crossmab TCR-scFv fusion Crossmab epcoritamab (DLBCL) Approved in the US in 2023 DuoBody 2+1 Crossmab |
• High expectations for targeted T cell therapies in cancer, but often: – Narrow therapeutic window: – Cytokine Release Syndrome – On-target/off-tumor-related toxicities – Activates immunosuppressive T cells – Sporadic efficacy in solid tumors therapeutic window therapeutic effect toxic effect ©LAVA Therapeutics 2023 8 Enthusiasm for Bispecific T Cell Engagers |
• Selecting ‘tumor-specific’ targets • Step-dosing / subcutaneous dosing • Decreasing affinity for T cells • Masking/site-specific activation • Recruiting alternative effector cells • Address only narrow target range, and/or • Cumbersome, and/or • Strongly decrease potency ©LAVA Therapeutics 2023 9 Strategies for Widening the Therapeutic Window |
Bispecific T cell-engagers aim to harness innate & adaptive immunity • Largest -T cell subset in blood: (~90-95% of total γδ-T cells) • Natural ability to recognize and kill tumor cells • Presence of T cells associated with improved outcomes in cancer patients • Recognize tumors through phosphoantigen-BTN2A1/3A1 complex • Consistent pro-inflammatory cytotoxic effector T cell population ©LAVA Therapeutics 2023 10 Innate Immunity Adaptive Immunity Adapted from Dranoff G., Nature Rev. Cancer 2004; 4: 11-22 |
Systemic Activation of V9V2 T Cells Showed Promise • Systemic activation and proliferation via treatment with V9V2 T cell-based therapy (synthetic phosphoantigens (BrHPP) / aminobisphosphonates ± low-dose IL-2) Early attempts with V9V2 T cell-based therapy showed promise, but efficacy may have been limited by systemic, non-tumor specific activation of V9V2 T cells and exhaustion ex vivo activation in vivo activation • Clinical trials with in/ex vivo activation protocols showed promising objective responses and safety • No signs of high grade cytokine release syndrome (CRS) as a result of V9V2 T cell activation cell transfer therapy isolation of T cells Tumor Pre-Treatment Post-Treatment Lung metastases of RCC; adoptive transfer Lymphoma; NBP / IL-2 Kobayashi H et al., Cancer Immunol Immunother 2011; 60: 1075-1084 Wilhelm M et al., Blood 2003; 102: 200-206 ©LAVA Therapeutics 2023 |
Off-the-Shelf Gammabody® Platform: Designed to Enhance Innate Tumor Recognition by Directing V9V2 T Cells to the Cancer Cells LAVA’s Gammabody® designed ti directs V9V2 T cells to tumors to induce direct tumor cell killing with high potency and has the potential to trigger a cascade of anti-cancer immune responses while retaining tumor selectivity V9V2 T cells recognize stress signals TCR interacts with pAg-butyrophilin complex Conditionally activate V9V2 T cells upon crosslinking with tumor associated antigen (TAA) Gammabody® Designed to Provide Tumor Recognition to Trigger V9V2 T Cell-Mediated Immunity Retains recognition of natural stress signals Natural Activation Mechanism ©LAVA Therapeutics 2023 12 ® |
Cascade of Anti-Cancer Responses – Potential Translation to Favorable Therapeutic Window Efficacy: • Potent killing of cancer cells (EC50s in the low picomolar range) • No co-activation of immune-suppressive Tregs which dampen antitumor efficacy of cytotoxic T cells • Orchestrate innate and adaptive immune responses, potentially resulting in potent and durable responses • Activity against hematologic malignancies and solid tumors, including immunologically “cold” tumors • Potential for expansion of V9V2 T cells can result in an increased number of anti-tumor V9V2 T cells in the tumor Safety: • Conditional activation with high accuracy • Greatly reduced potential for cytokine release syndrome (CRS); No evidence of CRS in NHP studies Adapted from Dranoff G, Nature Rev Cancer 2004; 4: 11-22 Kabelitz D et al., Cell Mol Immunol 2020; 17: 925–939 ©LAVA Therapeutics 2023 13 |
Gammabody® can induce robust gamma delta T cell expansion and can amplify the anti-tumor immune response via downstream activation of other immune cells while avoiding co-activation of immunosuppressive T cells such as Tregs Expansion Cascade Response No Treg Activation Gammabody™ - Mediated Expansion of V9V2 T Cells no bsTCE CD1d Gammabody™ CD40 Gammabody™ A431 Treg EGFR-CD3 TCE EGFR Gammabody™ Data on file: LAVA Therapeutics N.V. ©LAVA Therapeutics 2023 14 Expansion & Cascade Response Without Treg Activation in Preclinical Models |
• 2:1 ratio ( T cells : Target cells) • Similar CD20 expression levels on C1R neo and B-cells Preferential killing of cancer versus healthy cells demonstrated in vitro and ex vivo; May prevent on-target/off-tumor mediated toxicity and allow for targeting of widely expressed tumor associated antigens Prostate Cancer Normal Prostate Medium + PSMA Gammabody™ + V9V2 T cells + V9V2 T cells + PSMA Gammabody™ *** p<0.001 Data on file: LAVA Therapeutics N.V. ©LAVA Therapeutics 2023 15 Gammabody® Can Selectively Kill Cancer Cells While Sparing Healthy Cells in Hematologic Malignancy and Solid Tumor models CD20 Gammabody® Mediated Killing PSMA Gammabody® Mediated Killing |
LAVA-1207 Gammabody® Designed to Activate V9V2 T Cells by Targeting PSMA for the Treatment of mCRPC |
LAVA-1207: PSMA-targeting Gammabody® for Prostate Cancer Format • Contains a Fc domain for extended plasma half-life; silenced to avoid off-target T cell activation • Small size (compared to regular IgG antibodies) to facilitate tumor penetration Mechanism of Action • Specifically directs V9V2 T cells to PSMA-expressing tumor cells – PSMA is a well-validated tumor target • Mediates potent killing of PSMA-positive tumor cells • Preclinical data support mechanism of action, anti-cancer activity & selectivity Status • Phase 1/2a trial in mCRPC; patient recruitment ongoing (NCT05369000) Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 17 10 -3 10 -2 10 -1 10 0 10 1 10 2 10 3 10 4 0 50 100 150 concentration LAVA-1207 (pM) % specific killing PC-3 (PSMA-neg) LNCaP (PSMA-high) LNCaP-PSMA KO |
18 Prostate Cancer Epidemiology Cancer.Net® FMI (Future Market Insights) ©LAVA Therapeutics 2023 Prostate Cancer − Most frequently diagnosed cancer in males (estimated 288,300 in the United States in 2023) − Second leading cause of cancer deaths in males (estimated 34,700 in the United States in 2022) − ~50,000 prevalent cases mCRPC − 5-year survival mCRPC ~30% − Est. CRPC market value ~$11 billion in 2023 PSMA • Overexpressed in >90% prostate cancers; low expression normal tissues • Increased expression mCRPC vs CSPC • Higher levels negatively correlated with survival outcomes • Clinically validated - Pluvicto (lutetium-177-PSMA-617 radioligand) FDA approved March 2022 |
19 mCRPC – Existing Treatment Options ©LAVA Therapeutics 2023 PARPi’s monotherapy or in combination in BRCAmut +ve 1L (~30,000) Docetaxel or androgen receptor pathway inhibitor (ARPI) (abiraterone, enzalutamide) 2L (~20,000) Docetaxel or ARPI (depending on prior treatment) 3L+ (~10,000) Cabazitaxel, lutetium-PSMA, sipuleucel-T |
20 PSMA-Selected Targeted Agents Landscape ©LAVA Therapeutics 2023 PSMA-targeted radioligands Drug Study Patient Population N Clinical Results Common Adverse Events Current Status 177Lu-PSMA vs BSOC VISION mCRPC post 1+ ARPI and 1+ taxane 551 vs 280 ORR: 30 vs 2% PSA50: 46 vs 7 % Median OS: 15.3 vs 11.3 mo Median rPFS: 8.7 vs 3.4 mo Fatigue (43%), dry mouth (39%), nausea (35%), anemia (32%), decreased appetite(21%) Approved 177LU-PNT2002 SPLASH Prior ARPI. No prior chemo 27 PSA50: 42% Dry mouth (25.9%), nausea (18.5%), fatigue (18.5%), hematuria and anemia (11.1%) Phase 3 Fast-track designation Anti-PSMA bispecifics AMG160 Anti-PSMAxCD3 Phase 1 mCRPC post-ARPI9s) and taxane(s) 35 PSA50: 34.3% ORR: 13.3% CRS (84%) Discontinued Replaced by AMG340 JNJ-63898081 Anti-PSMAxCD3 Phase 1 CRPC, 1+ prior therapies 39 PSA50: 2/39 (5.1%) Pyrexia (69.2%), CRS (66.7%), chills (46.2%), fatigue (41.0%) Discontinued HPN-424 Anti-PSMA xCD3xalbumin Phase 1/2a mCRPC >2 prior systemic therapies 80 PSA50: 3/80 (3.8%) Treatment >24 weeks: 24% CRS (63%) Grade 3+ AEs: AST increase (18%), ALT incr. (11%), anemia (11%) Discontinued REGN5678 + cemiplimab Anti-PSMAxCD28 Phase 1/2 CRPC, two prior lines including an ARPI 35 ORR: 3/8 evaluable PSA50: 4/35 (11.4%) CRS 6/35 (17.1%) irAEs >grade 3: 4/35 (11.4%) Continuing dose escalation |
LAVA-1207 – Phase1/2a Study Design 21 • Dose escalation in patients with mCRPC (EudraCT 2021-001789-39; NCT05369000) • Primary objectives: investigate safety and tolerability of LAVA-1207 • Secondary objectives: evaluate PK, PD, immunogenicity and preliminary signs of antitumor activity • LAVA-1207 administered via IV infusion every 2 weeks • Investigating combination with low dose IL-2 ASCO GU 2023 abstract #153 Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 |
LAVA-1207 – Patient Baseline Characteristics 22 N=20 ASCO GU 2023 abstract #153 Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 Data cut-off date: 8 Dec 2022 Patient Baseline Characteristics Age, median (range) 68 (51-76) Years since diagnosis, median (range) 9 (3-21) Prior systemic therapies, median (range) 4 (3-10) Location of metastases Bone 19 Lymph node 14 Lung 2 Liver 5 Other visceral 2 Type of progression PSA 17 Bone 12 Nodal 12 Visceral 10 |
LAVA-1207 – Time on Treatment ASCO GU 2023 abstract #153 Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 23 • Patients were treated with LAVA-1207 with treatment duration ranging from 4 to 38 weeks • Subsequent to ASCO GU 2023 presentation, LAVA has completed recruitment for dose levels 6 (± IL-2) and 7 monotherapy • Data cut-off date: 8 Dec 2022 23 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 N307 N306 N105 - N305 N304 N303 - N104 N206 N302 - U105 U104 N205 N301 N202 - U103 U102 U101 N101 N102 N201 Time since first study treatment (weeks) DL 1 1.5 μg DL 2 4.5 μg DL 3 13.5 μg DL 4 40 μg DL 5 120 μg Pt refused further treatment with IMP PD PD 12 cycles completed PD PD PD PD PD PD PD PD Clinical progression in absence of formal disease progression EoT Ongoing PD PD |
0 20 40 60 Fatigue Fever Nausea Anemia Constipation Back pain Pain AST increase Alkaline phosphatase increase Vomiting Anorexia Fall Tumor pain Hematuria Tingling Infusion related reaction Diarrhea Dry mouth Dyspepsia Dyspnea Edema Cytokine release syndrome Chills Flu-like symptoms Hot flashes Hypertension Hypocalcemia Lymphocyte count decreased LDH increase Lung embolism Urinary tract obstruction Urinary tract infection Frequency (%) Grade 1 Grade 2 Grade 3 N=20 60 40 20 All TEAE >5%, by grade TEAE suspected to be related >5%, by grade LAVA-1207 – Initial Phase 1 Data - Safety 24 • Favorable safety profile to date, with no occurrence of high-grade (>2) cytokine release syndrome or dose-limiting toxicities • Most observed AEs not suspected to be related and no DLT • Treatment emergent AEs (TEAEs) that were suspected to be related were grade 1 or 2 • No increase in severity or frequency of TEAEs with increasing doses and no patient discontinued treatment due to AE • One grade 4 AE occurred (spinal cord compression, DL 5), which was non-related • Data cut-off date: 8 Dec 2022 ASCO GU 2023 abstract #153 Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 |
LAVA-1207 – Pharmacokinetics • Pharmacokinetics of LAVA-1207 appears linear • Data cut-off date: 8 Dec 2022 25 0 24 48 72 96 120 144 168 1,000 10,000 Dose level 4 Time since infusion start (h) LAVA-1207 (ng/L) 5000 N303 N304 N305 0 24 48 72 96 120 144 168 1,000 10,000 Dose level 5 Time since infusion start (h) LAVA-1207 (ng/L) 30,000 N105 N306 N307 0 500,000 1,000,000 1,500,000 2,000,000 120 Dose vs. AUC for Cycle 1 Dose (μg) AUC(0-∞ ) (h*pg/mL) Subject ID N202 N301 N104 N206 N302 N303 N304 N305 N105 N306 N307 4.5 13.5 40 DL 2 DL 3 DL 4 DL 5 ASCO GU 2023 abstract #153 Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 |
LAVA-1207 – Pharmacodynamics • Pharmacodynamics reflect changes expected as per MoA − Pronounced drop in V9V2-T cell frequency 2 hr after dosing, suggesting V9V2-T cell re-distribution, with subsequent recovery − V9V2-T cell activation markers (CD25 and CD69) upregulated following dosing − Receptor occupancy detectable up to day 14 after EoI, with peak levels ranging from 6.1% to 12.6% • Data cut-off date: 8 Dec 2022 26 0 2 4 6 8 10 0 50 100 150 25 50 Vγ9Vδ2 T cells - % of CD45 Change compared to predose Time since first study treatment (days) Relative change (%) 0 2 4 6 8 10 0 10 20 25 50 Vγ9Vδ2 T cells - % LAVA-1207 receptor occupancy Treatment day %RO 0 2 4 6 8 10 0 10 20 30 40 25 50 Vγ9Vδ2 T cells - % CD25+ Time since first study treatment (days) %CD25+ 0 2 4 6 8 10 0 20 40 60 80 100 25 50 Vγ9Vδ2 T cells - % CD69+ Time since first study treatment (days) %CD69+ N304 N305 N303 dosing ASCO GU 2023 abstract #153 Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 Dose level 4 – 40 µg |
LAVA-1207 27 Preliminary signs of anti-tumor activity were observed, with iRECIST stable disease (iSD) in 8 out of 14 evaluable patients at week 8 and PSA levels stabilizing or decreasing in heavily pre-treated patients 27 Patient N304 – 40 g • Largest overall decrease in PSA was 61% (46% vs baseline) • Per treating physician, the patient improved clinically with improvement in pain and fatigue • Data cut-off date: 8 Dec 2022 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 -50 0 50 100 PSA change from C1D1 (%) 220 198 191 147 133 129 120 0 2 4 6 8 10 12 14 0 200 400 600 800 Time since first study treatment (weeks) PSA (μg/L) ASCO GU 2023 abstract #153 Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 Best PSA response PSA levels – Pt N304 Cohort 4 |
28 T cell TCR triggering: upregulation of high-affinity IL-2R Addition of IL-2 supports Gammabody® induced Vγ9Vδ2 T cell proliferation IL-2 binds to IL-2R complex and promotes proliferation IL-2 supports Gammabody® induced expansion of V9V2 T cells ©LAVA Therapeutics 2023 IL-2 immunomodulation has the potential to boost V9V2 T cell counts and could further enhance clinical responses V9V2 T cells Gammabody Gammabody +IL-2 14-day co-culture of tumor cells and PBMC in the presence of Gammabody® ± IL-2. E:T = 10:1 |
Summary of Initial Phase 1 Data • LAVA-1207 reached a dose of 120 g (starting dose 1.5 g) without the occurrence of high-grade (>2) CRS or DLTs in therapy refractory mCRPC patients – Frequency and severity of AEs do not appear to be dose-dependent – Most observed AEs were not suspected to be related • Preliminary signs of clinical activity observed with disease stabilization and PSA reduction during dose escalation • Pharmacodynamics reflect changes as expected per MoA • Dose escalation continues in both Europe and the United States • IL-2 immunomodulation will be explored in additional parallel cohorts • Expect to release data within 12 months 29 ASCO GU 2023 abstract #153 Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 |
LAVA-051 Targets CD1d to Activate V 9V2 T Cells and iNKT Cells for the Potential Treatment of CLL, MM & AML |
Format • Humanized bispecific single domain antibody (bsVHH) of 27kDa ‒ Short plasma half-life, prolonged functional half-life through high affinity TCR binding Mechanism of Action • Engages V9V2 T cells to mediate potent killing of CD1d-expressing tumor cells – CD1d is expressed on tumor cells in CLL, MM and AML – Activates iNKT cells to mediate the killing of CD1d-expressing tumor cells as a secondary mechanism of action – Preclinical data support mechanism of action, anti-cancer activity, effector cell expansion and tumor selectivity LAVA-051: First-in-Class Gammabody® Targeting CD1d 31 Lameris R, et al Nature Cancer 2020 Lameris R, et al Cell Rep Med 2023 Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 |
02 4 6 8 0.0 0.2 0.4 0.6 0.8 1.0 20 40 60 80 100 120 V9V2 T cell frequency Cohort 2 pt 02-001 Treatment days % of CD3+ 0 2 4 6 8 12 0 20 40 60V9V2 T cell activation Cohort 2 pt 02-001 Treatment days % CD25+ 0 2 4 6 8 0 5 10 15 20 25 V9V2 T cell RO Treatment days %RO 3 μg 15 μg 45 μg (1 pt) 32 LAVA-051 – Phase 1 Data Confirms MoA in Patients with MM and CLL • Pharmacodynamic parameters reflect changes expected for the LAVA-051 mechanism of action – V9V2 T cell activation markers (CD25 and CD69) upregulated following dosing – Maximum V9V2 T cell receptor occupancy (RO) increased with escalating dose – iNKT cell activation was assessable, and observed, in one patient • Data cut-off date: 11 Nov 2022 ASCO 2022 abstract 2577; ASH 2022 abstract #2014 Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 • Favorable safety profile in doses up to 200μg − No CRS and no ICANS (ASTCT) and no clinically relevant increase in the CRS-related cytokine IL-6 |
LAVA-051 – Potential Signs of Activity CLL • Patient with R/R CLL (15 g) • Temporary enlargement and tenderness of several involved lymph nodes accompanied by grade 2 fever during Cycle 1 ‒ Resembled a tumor-flare reaction, as reported in CLL with lenalidomide • Patient assessed as having stable disease • Percent of clonal B cells in peripheral blood decreased • Numbers of CD1d expressing monocytes remained similar MM • High-risk MM patient (45 g) • 4 prior lines of therapy within 6 years from diagnosis • Refractory to last 3 lines of treatment • 23% reduction in M-protein Both patients ceased treatment due to COVID-19 EHA 2002 abstract #1463 R/R = Relapsed/Refractory Permission for photo obtained Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 0 25 50 75 100 125 0.01 0.1 1 Treatment days Cell count (x10 9 /L) Lymphocytes Clonal B cells Monocytes 33 |
LAVA-051 – Preliminary Conclusions • Phase 1 trial supports MoA and safety of the Gammabody® platform − Binding and activation of V9V2 T cells and associated effects on tumors • Trial for relapsed or refractory CLL and MM to be discontinued − Trial ended due to challenging enrollment; highly competitive space − No safety concerns contributing to decision to discontinue the study − No longer recruiting − Will be terminated when all patients have completed treatment − Complete Phase 1 clinical trial data to be presented when final patients end treatment ©LAVA Therapeutics 2023 34 |
SGN-EGFRd2 (LAVA-1223) – Licensed to Seagen Gammabody® for the treatment of EGFR-expressing solid tumors |
SGN-EGFRd2 (LAVA-1223) – EGFR-Targeting Gammabody® Format • Gammabody® containing a silenced Fc domain Mechanism of Action • Induces preferential lysis of EGFR-expressing tumor cells while relatively sparing EGFR-expressing normal cells Status • IND cleared • Phase 1 Study in Advanced Solid Tumors expected to begin 2023 • Exclusive worldwide license agreement with Seagen Inc. • Seagen to develop and commercialize SGN-EGFRd2 (LAVA-1223); potential for milestones of up to approximately $650 million and royalties 36 King L, et al. Cancer Immunol Res 2023, in press Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 – Licensed to Seagen Patient derived tumor tissue Patient derived non-tumor tissue |
Janssen Collaboration Lead Candidate in Development Toward Clinic |
Janssen Collaboration 38 • Lead candidate, aimed at an undisclosed tumor-associated antigen, has been chosen for further development toward clinical studies − In May 2020, LAVA entered into a research collaboration and license agreement with Janssen for the discovery and development of a novel bispecific gamma-delta T cell engager for the treatment of cancer • Janssen is responsible for the future clinical development, manufacture, and commercialization of the candidate at Janssen’s sole cost and expense • Product candidate onboarded June 2023 • LAVA is eligible to receive development, regulatory and commercialization milestone payments and royalties Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 2023 – Licensed to Janssen |
CD123 Targeting Gammabody® for the Treatment of Hematologic Malignancies LAVA-1266 |
• In Development for Treating Hematological Malignancies • Mechanism of Action − Induces preferential lysis of CD123-expressing tumor cells while relatively sparing CD123-expressing normal cells • CD123 is overexpressed in a wide range of hematological malignancies LAVA-1266: CD123-Targeting Gammabody® Data on file: LAVA Therapeutics N.V ©LAVA Therapeutics 20230.01 0.1 1 10 100 1000 0 20 40 60 80 100 LAVA-1266 concentration [pM] Specific cell death (%) EC50 ~ 8 pM Potent lysis of primary AML cells 0.01 0.1 1 10 100 1000 0 20 40 60 80 100 LAVA-1266 concentration (pM) Specific cell death (%) CD123+ tumor cell line CD123+ healthy cells (donor 1) CD123+ healthy cells (donor 2) Preferential lysis of tumor cells 40 • Status − IND/CTA enabling activities ongoing, expected to be ready 1H 2024 |
Anticipated Milestones & Recent Updates |
MM: multiple myeloma CLL: chronic lymphocytic leukemia AML: acute myeloid leukemia PSMA: prostate-specific membrane antigen EGFR: epidermal growth factor receptor mCRPC: metastatic castration-resistant prostate cancer Gammabody® Pipeline: Potential in Hematological and Solid Tumor Indications 42 ©LAVA Therapeutics 2023 Candidate Target Indication(s) Discovery Preclinical Phase 1 Phase 2 Anticipated Milestones & Recent Updates LAVA-1207 PSMA mCRPC • Most recent data released: ASCO GU 1Q 2023 • Next data release expected within 12 months LAVA-051 CD1d MM CLL AML • Enrollment has been discontinued • Complete Phase 1 clinical trial data to be presented when final patients end treatment SGN-EGFRd2 (LAVA-1223) EGFR Solid Tumors • Licensed to Seagen 3Q 2022 • IND cleared • Phase 1 Study in Advanced Solid Tumors expected to begin 2023 Janssen Collaboration undisclosed • Lead candidate selected by Janssen 2Q 2023 LAVA-1266 CD123 Hematologic Malignancies • IND/CTA enabling activities ongoing, expected to be ready 1H 2024 LAVA-1278 CD40 Hematologic Malignancies Hematologic malignancy Discontinued Solid Tumor Undisclosed |
Gamma-delta T cell engagers for the development of next-generation cancer therapeutics Corporate Presentation August 2023 |