Lunai Bioworks Inc. · NASDAQ:LNAI
Lunai Bioworks — Innate Killer Summit 2022
17 slides from Lunai Bioworks's conference presentation, March 2022
Slide 1: Innovating Novel Clinical Protocols for Gamma Delta T, NK and Dendritic Cell Combination Therapy
Innovating Novel Clinical Protocols for Gamma Delta T, NK and Dendritic Cell Combination Therapy in Solid Tumors and HIV Serhat Gumrukcu, M.D., Ph.D. March 2022 Innate Killer Summit, San Diego, CA
Slide 2: Disclosures
Disclosures Ø Enochian Biosciences Ø Pyrus Bio Ø Frida Therapeutics
Slide 3: Brief History of Adoptive Cell Therapies
Brief History of Adoptive Cell Therapies Ø The first historical example of adoptive cell therapy outside of HSCT was performed in 1986 with a positive clinical outcome in a patient with MRD of acute lymphoblastic leukemia (ALL), which was eventually named as donor lymphocyte infusion (DLI). (Slavin
Slide 4: Brief History of Adoptive Cell Therapies
Brief History of Adoptive Cell Therapies Ø Following his case, many oncologists around the world reported the effectiveness of DLI in patients with cancer cells resistant to conventional chemotherapies. Ø Subsequently, it became a standard therapy for recurrent hematologic malignancies and paved the
Slide 5: Factors Affecting Clinical Outcome
Factors Affecting Clinical Outcome Ø Stage of disease, or more importantly, timing of the cell therapy MRD Ø Immunological baseline of the patient (immune perturbations caused by cancer, side effects of chemotherapy, immunotherapy, and/or radiation therapies) Ø Preconditioning regimen (lympho-deplet
Slide 6: Modern use of NK cells- Clinical protocol example
Modern use of NK cells- Clinical protocol example Lympho-depletive chemotherapy (Flu or Cy) Intentionally mismatched ex vivo activated NK cell infusion In vivo administration of rIL-2 for continuous cell activation COX-2 inhibitor to reduce Treg differentiation
Slide 7: Past Clinical Outcomes
Past Clinical Outcomes* *Gumrukcu et al, Seraph Research Institute and collaborators’ single-patient studies or treatment INDs (2014-2022)
Slide 8: Clinical Example 1 – Patient History
Clinical Example 1 – Patient History Ø 36-yo male Ø Recurrent bilateral Glioblastoma (GBM) with subtotal tumor resection (July 2019) Ø Standard therapy for recurrent GBM -> Chemotherapy (temozolomide) and radiation, 6 months Ø Mean time to tumor recurrence in gross total resection - > 9.3 months Ø O
Slide 9: Clinical Example 1 – Clinical Outcome
Clinical Example 1 – Clinical Outcome Ø No visible residual lesion in perfusion MRIs starting Oct 2019 Ø Complete remission: 29 months since remission achieved, 26 months since the end of therapy Ø As of 12 months of remission, tumor-specific (CMV-pp65-specific) T cell clones persistent in the patie
Slide 10: Clinical Example 2 – Patient History
Clinical Example 2 – Patient History 2014 to 2020 Ø 8.5-yo female Multiple lines of chemotherapy and partial resection Ø Optic pathway glioma surgeries Ø History of multiple chemotherapy regimens February 2021 Ø History of multiple surgeries Partial resection and cyst drainage due to severe Ø Last s
Slide 11: Clinical Example 2 – Clinical Outcome
Clinical Example 2 – Clinical Outcome* Ø Reduction in cyctic formation around the tumor. Reduction in tumor size and viability by perfusion MRI and spectroscopy Ø Clinical improvement in muscle coordination. Nov 2021 Feb 2022 *Unpublished data. Seraph Research Institute, Los Angeles CA
Slide 12: Clinical Example 2 – Clinical Outcome
Clinical Example 2 – Clinical Outcome 3 Ø Clinical improvement in vision and visual acuity. (light perception improved, color and shape perception developed first time) Ø Reconstitution of endogenous lymphocyte and NK populations including improvement in function. Nov 2021 Feb 2022 *Unpublished data
Slide 13: Clinical Outcome – IFNg and PBMC analysis
Clinical Example 2 – Clinical Outcome* Feb 2021 BEFORE AFTER 124e6 PMBCs in 20ml whole blood PBMC (1:10) P128 SR PBMC (1:10) H289 SG H290 CP P128 SR H229 TC NK 4.28% 9.43% 1000 2500 CD4 28.3% 36.1% CD8 19.5% 31.0% 2000 CD19 36.9% 9.77% CD14 11.2% 20.2% IFNg(pg/ml) IFNg (pg/ml) total 100.18% 106.5% 1
Slide 14: Clinical Example 2 – Clinical Outcome
Clinical Example 2 – Clinical Outcome* BEFORE PBMC AFTER 50 60.00 P128 SR H229 TC H289SG H290CP 50.00 Lu30/106 cells Lu30/ 106 cells 40.00 30.00 20.00 10.00 0 0.00 Untreated IL-2 treated IL-2+anti-CD16 IL-2 + anti- IL-2 + sAJ2 IL-2 + anti-PD- untreated IL2 IL2+anti-CD16 IL2+anti-CD3/28 IL2+sAJ3 trea
Slide 15: Clinical Example 3
Clinical Example 3 Ø 54-yo male Ø HIV since 1986 Ø History of monotherapy, dual therapy, etc Ø Uncontrolled low viremia under combination ART (VL ~2,000 copies) Ø Low dose lympho-suppressive pre-condition regimen for 3 days (day -5 to day -2) Ø 25x106/kg NK cells and 5x106/kg gd-T cells on day 0 fro
Slide 16: Conclusion
Conclusion Ø Allogeneic primary NK therapies are safe, and can be very effective when they are administered at a favorable time (MRD stage in cancer patients, controlled or partially controlled viremia in HIV) and when the clinical protocol is tailored to overcome certain shortcomings of cell therap
Slide 17: Thank you!
Thank you! Serhat Gumrukcu, MD PhD Tae-Wook Chun, PhD Anahid Jewett’s Lab Phillip Musikanth, MD W. David Hardy, MD Tung X Nguyen Wenshi Wang, MD PhD Rachel White, PA-C Samantha Cherin, MSN ACNP CNS California Institute of Regenerative Gregory Howell Mark Dybul, MD and Cellular Medicine Adiela Pineda