BioEquity
3 days ago
PIPE Investors in SNTI paid $1.05/share last week! Reminder that $3.90/share is still equivalent to a $230M valuation for SNTI, vs $9M valuation last month! (See below, massive dilution in between.) Meanwhile, an institutional investor just purchased 4.2M shares and 6.3M warrants = 10.5M shares @ $1.05/share last week. Total is now ~60M shares outstanding on a fully diluted basis. The total # of shares just increased from 5M last month to 60M, meaning retail investors were diluted >10x, in addition to the 10:1 reverse stock split in July 2024. New PIPE investors did not pay $230M for SNTI, they paid about $65M, $1.05/share last week!
Read the actual SEC filing, not the press release from the company, which is misleading. (Why is each "Series A" share purchased convertible into 1,000 common shares, if not to disguise the massive dilution of this financing and the actual price paid by PIPE investors?) The main points are:
1/ A private investor purchased 10.5M shares last week for $10M at an effective share price of $1.05 while retail investors are expected to pay $3.90/share right now, at exactly the same time...
2/ The daily volume (150,000 shares/day) is very small. It doesn’t take more than one of the new hedge fund investors to decide to slowly sell off or short the stock from their initial investment (to “take money off the table”) and they would still retain 80% of the upside. This is a relentless downward pressure on the stock, notwithstanding short term volatility.
3/ The effective valuation of the company is $230M! Meanwhile, a sophisticated new investor is buying in at $65M ($1.05/share * 60M shares). Either this sophisticated investor is getting the deal of the century (which is unlikely in a competitive market for capital) or retail investors are still massively overpaying right now at a $230M valuation = $3.90/share!
Press Release (somewhat misleading re: dilution): SNTI Press Release
SEC filing here: Legal SEC Filing
Institutional investors purchased shares last week at about $1.05/share. This is the fair market value. Retail investors are massively overpaying at $3.90/share
subslover
1 month ago
Senti Biosciences, Inc. Announces Oversubscribed $37.6 Million Private Placement Equity Financing
SOUTH SAN FRANCISCO, Calif., Dec. 02, 2024 (GLOBE NEWSWIRE) -- Senti Biosciences, Inc. (Nasdaq: SNTI) (“Senti Bio” or the “Company”), a clinical-stage biotechnology company developing next-generation cell and gene therapies using its proprietary Gene Circuit platform, has entered into a securities purchase agreement with certain existing and new accredited investors to issue and sell an aggregate of 16,713 shares of Series A Convertible Preferred Stock (the “Preferred Stock”) through a private investment in public equity (the “PIPE”) financing. Senti Bio anticipates the gross proceeds from the PIPE financing to be approximately $37.6 million, before deducting offering expenses. In addition, investors, upon receipt of stockholder approval by the Company’s stockholders, will have the right to exercise warrants to purchase up to an additional 25,069,500 in shares of the Company’s common stock. The PIPE financing is anticipated to close on or before December 5, 2024, subject to customary closing conditions. The Company has also granted to a certain investor an option to purchase an additional 4,444 shares of Preferred Stock and accompanying warrants for gross proceeds of approximately $10.0 million at a subsequent closing to occur no later than December 27, 2024.
The PIPE financing was led by Celadon Partners, with participation from New Enterprise Associates (NEA), Leaps by Bayer, Nantahala Capital, The Red Hook Fund LP, and other institutional and accredited investors. The Company intends to use the net proceeds from the offering, together with existing cash, cash equivalents and investments, to fund the continued development of its SENTI-202 program and manufacturing ramp-up, other research and development activities, and for general corporate purposes.
Leerink Partners is acting as the placement agent for the PIPE financing.
The securities sold in the PIPE financing are being made in a transaction not involving a public offering and have not been registered under the Securities Act of 1933, as amended, and may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements. Concurrently with the execution of the securities purchase agreement, Senti Bio and the investors entered into a registration rights agreement pursuant to which the Company has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the common stock issued or issuable in connection with the PIPE financing.
This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. Any offering of the securities described above under the resale registration statement will only be by means of a prospectus.
About Senti Bio
Senti Bio is a clinical-stage biotechnology company developing a new generation of cell and gene therapies for patients living with incurable diseases. To achieve this, Senti Bio is leveraging a synthetic biology platform called Gene Circuits to create therapies with enhanced precision and control. These Gene Circuits are designed to precisely kill cancer cells, spare healthy cells, increase specificity to target cells and control the expression of drugs even after administration. The Company’s wholly-owned pipeline includes off-the-shelf CAR-NK cells, outfitted with Gene Circuits, to target challenging liquid and solid tumor indications. Senti Bio has also preclinically demonstrated that its Gene Circuits can function in T cells. Additionally, Senti Bio has preclinically demonstrated the potential breadth of Gene Circuits in other cell and gene therapy modalities, diseases outside of oncology, and continues to advance these capabilities through partnerships with Roche/Spark Therapeutics and Bayer/BlueRock Therapeutics.
Forward-Looking Statements
This press release contains certain statements that are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements generally are identified by the words “believe,” “could,” “predict,” “continue,” “ongoing,” “project,” “expect,” “anticipate,” “estimate,” “intend,” “strategy,” “future,” “opportunity,” “plan,” “may,” “should,” “will,”
subslover
1 month ago
Senti Bio Announces Positive Initial Clinical Data in Phase 1 Clinical Trial of SENTI-202, a Logic Gated, Selective CD33/FLT3-Targeting CAR-NK Cell Therapy for the Treatment of Relapsed/Refractory Hematologic Malignancies Including AML
– 2 of 3 patients achieved MRD negative CR in the first dose level evaluated in the trial with a generally well-tolerated preliminary safety profile –
– Dose escalation is continuing with additional response and durability data expected in 2025 –
– Conference call scheduled on December 3 at 7:30am ET –
SOUTH SAN FRANCISCO, Calif., Dec. 02, 2024 (GLOBE NEWSWIRE) -- Senti Biosciences, Inc. (Nasdaq: SNTI) (“Senti Bio” or the “Company”), a clinical-stage biotechnology company developing next-generation cell and gene therapies using its proprietary Gene Circuit platform, today reported positive initial clinical data from a Phase 1 clinical trial of SENTI-202, a potential first-in-class Logic Gated off-the-shelf chimeric antigen receptor natural killer (“CAR-NK”) investigational cell therapy, for the treatment of relapsed/refractory (“R/R”) hematologic malignancies including acute myeloid leukemia (“AML”). SENTI-202 is designed to selectively target and eliminate CD33 and/or FLT3- expressing hematologic malignancies, including AML, while sparing healthy bone marrow cells.
Three AML patients have been treated at the lowest dose level (1.0 billion CAR+ NK cells per dose) and, as of the data cutoff date of September 19, 2024, two achieved complete remission (“CR”), confirmed by bone marrow biopsy, which includes blast reduction and recovery of blood cells to normal ranges. In addition, both patients were assessed as measurable residual disease (“MRD”) negative after treatment, which is defined as no detectable cancer cells present in a bone marrow sample by the most sensitive locally available method. As of today, both patients continue to maintain their remission (4+ months and 3+ months, respectively). In all three patients, SENTI-202 was generally well-tolerated with an adverse event profile consistent with the use of lymphodepleting chemotherapy in patients with AML.
“R/R AML is a devastating disease that progresses rapidly with no approved therapies once it has progressed past first-line intensive or venetoclax-based treatment, or targeted agents in the subset of patients with addressable mutations,” said Kanya Rajangam, MD, PhD, President, Head of R&D and Chief Medical Officer of Senti Bio. “In the trial, early and deep responses at the first dose level were observed along with a generally well-tolerated preliminary safety profile, which is very encouraging. We look forward to reporting on additional response and durability data in 2025 as we continue dose finding.”
Stephen A. Strickland, Jr., MD, MSCI, Director, Leukemia Research for Sarah Cannon Research Institute, added, "Across the Sarah Cannon Research Institute network, we care for thousands of leukemia patients yearly and, given the limited treatment options for patients with R/R AML, we are constantly hoping for new therapies with novel mechanisms of action. I am very encouraged by the initial findings—these early clinical results suggest that SENTI-202 may potentially address the critical limitations of existing therapies and provide hope to people living with AML."
Clinical Results Summary (September 19, 2024)
As of the data cut, three patients with R/R AML were enrolled at the 1.0 billion CAR+ NK cells/dose level, administered three times, on days 0, 7, and 14 of a 28-day cycle following lymphodepletion with fludarabine/cytarabine (“Ara-C”)
The lowest dose cohort was cleared by the Safety Review Committee and dose escalation is continuing at the 1.5 billion CAR+ NK cells/dose level
Two patients achieved CR; one after two cycles and the other after one cycle, both with absent MRD by the most sensitive methods available for the patients at the respective clinical sites. With an additional two months of follow-up since the data cut, both patients are continuing to maintain MRD negative CR status (4+ months and 3+ months, respectively). One patient had no response after one cycle of treatment and was refractory to therapy
SENTI-202 was generally well-tolerated with no dose limiting toxicities (“DLTs”) and an adverse event profile consistent with other investigational NK cell therapies and patients with underlying AML receiving lymphodepleting chemotherapy
SENTI-202 transgene was detected in the peripheral circulation of all 3 patients and in all cycles, with a pharmacokinetic (“PK”) profile generally consistent with other investigational CAR-NK therapy levels
SENTI-202 Efficacy Data
3 doses/cycle (day 0, 7, 14) Number of Patients
1.0 billion CAR+ NK per dose 2/3 patients achieved CR
2/2 CRs are MRD negative*
* One assessed by Next Generation Sequencing and another by Multi-Parametric Flow Cytometry
SENTI-202 Safety Data
Key Adverse Events*
Patient 1 Grade 4 hematologic toxicity (thrombocytopenia)^
Grade 1 fever^ / Grade 2 bacteremia / Grade 3 upper respiratory infection (SAE)
No DLT/ AEI
Patient 2 Grade 4 hematologic toxicity (neutropenia & leukopenia)^
Grade 2 fever (reported as CRS)
No DLT / SAE
Patient 3 Grade 4 hematologic toxicity (pancytopenia)^
Grade 1 fever (reported as CRS)
No DLT / SAE
* Treatment emergent adverse events, regardless of relationship to SENTI-202; SAE (“Serious Adverse Event”); DLT (“Dose Limiting Toxicity”); Adverse Events of Interest (“AEI”) includes Cytokine Release Syndrome (“CRS”)
^ related to lymphodepletion
SENTI-202 Next Steps
The Company expects to enroll a total of approximately 20 patients in the Phase 1 trial, based on the current clinical trial design. A higher dose cohort of 1.5 billion CAR+ NK cells/dose is actively enrolling. Additional safety and efficacy data, including initial durability data, are expected to follow in 2025.
Conference Call Information
Senti Bio management and Dr. Strickland will discuss the SENTI-202 results on December 3, 2024 at 7:30am ET. To access the live webcast, please register online on the Events and Presentations page of Senti Bio’s website. The webcast may also be accessed as follows:
Conference ID: 1202759
United States - New York +1.646.968.2525
USA & Canada - Toll-Free +1.888.596.4144
Live webcast: https://edge.media-server.com/mmc/p/q37k42qa
An archived webcast and accompanying slides will be available on the Company’s website approximately one hour after the event.
About the Clinical Trial
The Phase 1 clinical trial of SENTI-202 (NCT06325748) is enrolling adult patients with R/R CD33 and/or FLT3 expressing hematologic malignancies, including AML, at multiple sites in the United States and Australia. The dose finding trial is currently evaluating two dose levels, either 1.0 billion or 1.5 billion SENTI-202 cells. SENTI-202 is administered in 3 weekly doses (Days 0, 7, 14) of a 28-day treatment cycle following a lymphodepletion conditioning regimen of fludarabine and cytarabine. Patients will receive a minimum of one and maximum of three treatment cycles. Patients may continue to receive multiple cycles of treatment based on safety and efficacy data. This trial is funded in part by the California Institute for Regenerative Medicine (“CIRM”).
About SENTI-202
SENTI-202 is a Logic Gated off-the-shelf CAR-NK cell therapy product candidate designed to selectively target and eliminate CD33 and/or FLT3 expressing hematologic malignancies, such as AML and myelodysplastic syndrome (“MDS”), while sparing healthy bone marrow cells. SENTI-202 has three main components. First, SENTI-202 contains an OR GATE, which is an activating CAR that recognizes CD33 and FLT3. By targeting either or both of these antigens, SENTI-202 is designed to effectively kill both leukemic blasts and leukemic stem cells, which constitute a difficult-to-eradicate reservoir of AML disease. Second, SENTI-202 contains a NOT GATE, which is an inhibitory CAR that is designed to recognize healthy cells and protect those healthy cells from being killed, thus potentially widening the therapeutic window. Third, SENTI-202 contains calibrated-release IL-15, which is designed to significantly increase cell persistence, expansion and activity of both the CAR-NK cells and host immune cells. The NK cells used to construct SENTI-202 are sourced from healthy adult donors, which have been screened based on a set of criteria that reflect manufacturability and product quality, and are then cryopreserved prior to use in manufacturing to minimize variability. Senti Bio is currently enrolling adult patients with R/R CD33 and/or FLT3 expressing heme malignancies in a Phase 1 clinical trial for SENTI-202, which can be a potential first-in-class allogeneic treatment for AML/MDS patients.
Senti Bio has published SENTI-202 preclinical data demonstrating the potential of Logic Gated CAR-NK cell therapy for the treatment of AML.
About AML
AML is a cancer of the blood and bone marrow and is the most common type of acute leukemia in adults. It is estimated there will be 20,800 new cases of AML in the United States in 2024. The five-year survival rate for these patients is approximately 30%. AML is currently treated with chemotherapy, targeted therapies, and/or allogeneic or autologous stem cell transplant. For patients with R/R AML, there are few treatment options and median overall survival is typically less than seven months.
About Senti Bio
Senti Bio is a clinical-stage biotechnology company developing a new generation of cell and gene therapies for patients living with incurable diseases. To achieve this, Senti Bio is leveraging a synthetic biology platform called Gene Circuits to create therapies with enhanced precision and control. These Gene Circuits are designed to precisely kill cancer cells, spare healthy cells, increase specificity to target cells and control the expression of drugs even after administration. The Company’s wholly-owned pipeline
jondoeuk
8 months ago
Discovery of Novel CARs for Solid Tumors Using Senti REVEAL™, a Massively Parallel Technology Platform Comprising Pooled Screening, Machine Learning, and Lab Automation
Introduction. CAR-T and CAR-NK therapies have limited efficacy in solid tumors due to multiple factors including the immunosuppressive tumor microenvironment and the limited potency of the signaling domains of current approved CAR therapies. More potent CAR signaling domains may address this limitation by activating different pathways (or combinations) that increase robustness to the immunosuppressive tumor microenvironment. FDA-approved CAR therapies for liquid tumors tend to use a limited set of intracellular domains, highlighting a need for new signaling domains for solid tumors. Conventional approaches of screening and optimizing CAR designs are manual labor intensive, low throughput, and can suffer from operator and batch error.
Methods. We developed a massively parallel technology platform, REVEAL™ (Research Engine for Validation of Engineered Asset Libraries), comprising (1) pooled screens of CAR libraries of 10,000s to 100,000s of signaling domains, (2) machine learning models to predict performance, and (3) parallel clonal validation of 100s to 1,000s of candidates using a purpose-built automated liquid handler. Here we used CAR-NK cells, but we anticipate that this framework can be used for other types of effector cells such as CAR-T. We designed libraries of CARs with a fixed extracellular domain targeting CEA, an antigen expressed on a range of solid tumors including colorectal cancer, and over 50,000 combinatorial signaling domains consisting of arrays of subdomains derived from native receptors. High-performing CARs in the libraries were discovered using a sort-seq approach: cells expressing CARs driving robust degranulation (CD107a+) were sorted, and CARs enriched in these cells were identified via NGS. We used these data to train machine learning models mapping CAR structure (i.e., the position and identity of constituent subdomains) to performance. In addition to reproducing experimental CAR performance, these models were used to predict CAR structures not present in the dataset due to cloning or coverage constraints. The highest performing library CARs and model-predicted CARs were then clonally validated in parallel using a liquid handler-based workflow that automated viral production, NK transduction, co-culture assay setup, and imaging-based readout of target killing.
Results. Our library screens and modeling indicate, and our clonal validations confirm, that signaling domains enriched for TRAF-binding motifs have high performance in the context of anti-CEA CAR-NK cells. Among highest performing CARs, however, TRAF domains are typically accompanied by other functional motifs, constituting a more diverse signaling array than would be found in a single native immune receptor. Successful CARs often comprised multiple canonical immune signaling types, i.e., signal 1 (CD3z), signal 2 (one or more costimulatory motifs) and signal 3 (cytokine signaling), demonstrating that a variety of signaling features can be successfully packaged into a single compact CAR. Additionally, these CARs contained sequences from a wide variety of sources outside of canonical CAR domains such as CD3z, CD28, 4-1BB, indicating the untapped potential for designing new CARs for solid tumors.
Conclusion. The REVEAL™ framework described here is capable of extensive optimization of CAR structures, and could potentially be applied to development of potent CAR cell therapies targeting solid tumors and hematologic malignancies beyond B cell cancers.
https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=60213
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