Fabio Tucci

For anyone building diagnostics: Very cool approach to gain valuable insights into FDA decision summaries. Brendan O'Leary scraped the FDA’s decision summaries and provided some simple R code for anyone to get up and running in no time to prod and probe those summaries. Very nice work!

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SDBN Feed: Candid Therapeutics unwraps three new collaborations to discover and develop T-cell engager antibodies https://lnkd.in/g4rKJTSk Candid Therapeutics, a new San Diego biotech bent on becoming a leader in the emerging T-cell engager space, has unwrapped three new research collaborations focusing on autoimmune diseases. Candid will partner with EpimAb Biotherapeutics, Nona [...]

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Bristol Myers Squibb has queued a Phase 1 study of Orum Therapeutics’ ORM-6151 (BMS-986497), a first-in-class, anti-CD33 antibody-enabled GSPT1 degrader for the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndromes. The study will enroll an estimated 35 patients and is due to start in late May 2024. Orum Therapeutics has developed a new class of ADC payloads, called neoDegraders, to specifically degrade intracellular target proteins within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, neoDegraders are designed to be delivered specifically to cancer cells and degrade the intracellular target protein and cause tumor cell death. https://lnkd.in/edTcDRFj

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Candid Therapeutics, a new San Diego biotech bent on becoming a leader in the emerging T-cell engager space, has unwrapped three new research collaborations focusing on autoimmune diseases. Candid will partner with EpimAb Biotherapeutics, Inc. , Nona Biosciences and Ab Studio to beef up its pipeline of bispecific antibodies. https://lnkd.in/eU4ktbC6

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Acurx Pharmaceuticals Announces Presentation of Ibezapolstat Phase 2 Clinical Trial Results for CDI at Scientific Conference   • Additional analyses of clinical and microbiological data from the Phase 2b segment show favorable gut microbiome changes including increased relative proportion of Actinobacteria in ibezapolstat-treated patients with C. difficile Infection (CDI) • Results consistent with those shown in earlier human volunteer studies and Phase 2a studies • Preservation and increased concentrations of beneficial Firmicute (Bacilotta) phylum known to be involved in bile acid homeostasis and short chain fatty acid metabolism was demonstrated  • Actinobacteria and Bacteroides preservation also confirmed using quantitative analysis   https://lnkd.in/eseFt8GZ   #nasdaq #acxp #antibiotics #acurx Acurx Pharmaceuticals, Inc. (Nasdaq: ACXP) David Luci

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A novel case of BiTE (EGFRxCD28) plus anti-PD-1: Targeting the 'right' patients counts! Colon cancer with microsatellite stability (MSS), 85% of patients¹, is non-responsive to anti-PD-1 therapy²⁻³. Recently, REGN7075, a EGFRxCD28 BiTE, plus anti-PD-1 showed encouraging efficacy, 6% (3/51) objective response rate (ORR); moreover, all responders were non-metastatic patients. Among the subset of non-metastatic patients (15), ORR became 20% (3/15)³. This validated our proposal that BiTE or anti-PD-1 or duo is more applicable to early-stage non-metastatic, instead of late-stage metastatic, solid-tumour cancer patients (see recent POSTs). The wild-type (WT) EGFRs are expressed on normal and cancer cells⁴, and colon cancer expresses WT EGFR⁵. A novel EGFR mAB targeted the epitope in Domain II (CR1) of extracellular domains⁵. The Domain II is masked in quiescent EGFRs of normal tissues, yet is exposed in EGFRs of cancer cells⁵. We deduced that REGN7075 also targeted the epitopes in Domain II, resulting in minimal on-target off-tumour toxicity of normal cells. TGN1412, a CD28 mAB, induced severe cytokine release syndrome⁶ (CRS); however, a novel CD28 mAB had shown lower CD28 affinity by targeting the epitope near the apex, instead of TGN1412's targeting the lateral epitope near cell membrane⁷. We deduced that REGN7075 also targeted the epitope near the apex of CD28, resulting in low CRS rate. By targeting novel epitopes of EGFR & CD28 presumably, REGN7075 incurred 35% of patients with grade 3/4 adverse events³ vs typical BiTE's 62-87%⁸⁻⁹. The CD3-based BiTE mimics signal 1 for T-cell activation by binding CD3. The CD28-based BiTE mimics signal 2 by binding the costimulatory CD28 receptor (ligands: CD80/86). The 'functional' DCs have become rare in tumour milieu and tumour itself does NOT emit danger signals to activate these rare DCs for upregulating CD80/86. Thus, there is the scarcity of CD80/86 (signal 2) in tumour milieu for properly 'reactivating' subprimed PD-1⁺ tumour-infiltrating T cells, which were initially 'subprimed' in lymph nodes by only signal 1 (see recent POSTs). By using anti-PD-1 (low dose) for T-cell 'reactivation'¹⁰ as signal 1 and CD28-based BiTE for direct CD28 binding as signal 2, the sub-primed PD-1ˡᵒʷ⁻ᶦⁿᵗ CD8⁺ T cells can resume cytotoxic effector function (granzymes and perforin) to kill tumours. Thus, Regeneron's novel duo of CD28-based BiTE plus anti-PD-1 is an encouraging therapy for early-stage non-metastatic colon cancer patients with MSS. 1. Brenner, Lancet, 2014 2. Lin, Cancer Immunol Immunother, 2023 3. https://lnkd.in/gH876tXN 4. S Khaznadar, Oncotarget 5. Gan, Cancer Res, 2012 6. S Suntharalingam, New Engl J Med 7. A Elsayed, MABS 8. Dickinson, New Engl J Med, 2022 9. Kantarjian, New Engl J Med, 2017 10. T Elliot, Immunity #Immunotherapy #ImmunoOncology #BiTE #PD1 #Costimulation #Pharmaceutical

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11 Antibody & 4 VHH full-platform transfers (Bayer, Bonum, Sanofi, Scholar Rock, Servier-Symphogen, UCB, EpiBiologics and others undisclosed). Now able to disclose Abbvie. Our libraries are popular. Jeff's talk explains why: high affinities, excellent developability, great diversities.

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Highlights the importance of taking biophysical properties into consideration in designing novel TKIs. FGFR2 specificity vs. FGFR1. Very cool findings in PNAS.

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Acurx Pharmaceuticals, Inc. (Nasdaq: ACXP) to Discuss Second Quarter 2024 Financial Results on August 9, 2024 Conference Call and Provide Business Update   Acurx Pharmaceuticals, Inc. (Nasdaq: ACXP), a clinical stage #biopharmaceutical company focused on developing new #antibiotics for difficult-to-treat #bacterial infections, has announced a conference call to discuss its second quarter 2024 financial results. The call is scheduled for August 9, 2024, at 8:00 am ET, before the U.S. financial markets open.   The company's President and CEO, David Luci, along with CFO Robert Shawah, will host the call to present the #financial results and provide a business update. #Investors and interested parties can join the call using the provided toll-free number for U.S. participants or international access numbers.   https://lnkd.in/esMuCywW #nasdaq #acxp #antibiotics #acurx Acurx Pharmaceuticals, Inc. (Nasdaq: ACXP) David Luci

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<!-- Content start --> South San Francisco, CA — July 3, 2024 — Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the Phase II/III SKYSCRAPER-06 study, evaluating tiragolumab plus Tecentriq® (atezolizumab) and chemotherapy versus pembrolizumab and chemotherapy as an initial (first-line) treatment for people with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (nSq NSCLC), did not meet its primary endpoints of progression-free survival (PFS) at its primary analysis with a hazard ratio (HR) of 1.27 [95% CI: 1.02,1.57] and overall survival (OS) at its first interim analysis with a HR of 1.33 [95% CI: 1.02, 1.73], which was immature. The combination of tiragolumab plus Tecentriq and chemotherapy showed reduced efficacy in both PFS and OS compared to the comparator arm in the intent-to-treat population, which includes Phase II and Phase III cohorts. The overall safety profile remains consistent with the safety profile previously observed for the combination of tiragolumab plus Tecentriq and chemotherapy, and no new or unexpected findings were identified. Based on these results, patients and investigators will be unblinded and we intend to halt the study. A communication will be sent to the investigators and results will be shared with health authorities and subsequently presented at an upcoming medical meeting. “These results are disappointing as it was our hope that this combination might yield improved outcomes for people living with metastatic non-squamous lung cancer,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We are thankful to all of the patients and healthcare professionals involved in the study, and we will leverage the learnings to inform our scientific understanding of the anti-TIGIT pathway and new avenues in cancer research.” Ongoing Phase III studies are investigating treatment settings and indications distinct from SKYSCRAPER-06. Based on today’s results, we will evaluate any relevant changes needed to the ongoing tiragolumab program. About SKYSCRAPER-06 study SKYSCRAPER-06 is a global Phase II/III, randomized, placebo-controlled and double-blinded study evaluating tiragolumab plus Tecentriq® (atezolizumab) and chemotherapy as an initial (first-line) treatment versus pembrolizumab and chemotherapy in 542 people with non-squamous non-small cell lung cancer. Primary endpoints are overall survival (OS) and progression-free survival (PFS). About tiragolumab Tiragolumab is an investigational novel immune checkpoint inhibitor with an intact Fc region. Tiragolumab selectively binds to TIGIT, a novel inhibitory immune checkpoint which suppresses the immune response to cancer. Based on preclinical research, tiragolumab is thought to work as an immune amplifier with other cancer immunotherapies such as Tecentriq® (atezolizumab). The TIGIT pathway is distinct but

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