−Removed: We are a clinical-stage oncology-focused cell therapy company that was historically involved in developing adoptive T-cell receptor, or TCR, engineered T-cell therapies, or TCR-T, designed to treat multiple solid tumor types in large cancer patient populations with unmet clinical needs.
+Added: We are a preclinical stage obesity and metabolic health drug development company that is aiming to develop a small molecule-based drug to treat obesity and other metabolic disorders that have a differentiated profile relative to currently marketed and in development oral and injectable products.
+Added: We believe ALN1001 and related small molecule product candidates are distinct in that they do not rely on hormonal manipulation, which is common with many obesity treatments.
+Added: We aim to develop an oral obesity compound that addresses many of the shortcomings of injectable GLP-1 receptor agonists including preserving lean muscle mass.
+Added: We engaged a contract development and manufacturing organization or CMDO to manufacture active pharmaceutical ingredients for our small molecule product candidates and initiated in vitro testing of our candidates in the fourth quarter 2024.
+Added: The ongoing in vitro study aims to evaluate the impact of ALN1001 and its derivatives on lipid deposition and gene expression.
+Added: This study evaluates if genes related to thermogenic activity, lipid metabolism, and energy regulation are activated or deactivated by treatment, to determine if these compounds positively affect fat and energy metabolism.
+Added: The results of this study, which are expected early second quarter of 2025, will provide critical insights into the development strategy for ALN1001 and its derivatives for obesity, metabolic disorders, and inflammation.
+Added: Drug development candidates most effective in increasing metabolic activity and reducing fat accumulation may be advanced to evaluation of the compounds in rodent models of obesity.
+Added: As is standard in the industry, if the aforementioned in vitro study is successful, we plan to conduct a proof-of-concept diet-induced obesity or DIO mouse study to validate our mechanism of action by the third quarter of 2025 before proceeding to Investigational New Drug or IND Application enabling studies.
+Added: Our ability to execute on this plan is dependent on study results and our ability to raise additional capital or partner these assets with other companies or research institutions.
+Added: Obesity Market
+Added: Obesity remains one of the most pressing public health challenges globally, with rates continuing to rise across many regions, particularly in the United States, Europe, and parts of Asia.
+Added: It is closely linked to a range of comorbid conditions, including type 2 diabetes, cardiovascular diseases, and certain cancers, which exacerbates the overall healthcare burden.
+Added: The obesity market is seeing increased attention, driven by growing awareness, better treatment options, and emerging scientific breakthroughs.
+Added: The global obesity market is experiencing rapid growth.
+Added: Globally, the market size for branded obesity drugs was $6 billion in 2023 and is estimated that it will reach $105.0 billion by 2030.
+Added: This growth is fueled by the rising obesity prevalence, evolving patient demographics, and increasing demand for effective weight-management solutions.
+Added: The shift toward more personalized treatments and the need for long-term weight management are key drivers of this growth.
+Added: The current treatment landscape for obesity consists of a combination of lifestyle interventions, pharmaceuticals, and surgical options.
+Added: Lifestyle interventions—dietary changes and physical activity—are the first-line treatment for most individuals, but many struggle to achieve and maintain significant weight loss through these methods alone.
+Added: Traditional weight-loss medications (e.g., OrlistatTM) are still used, though their side effects and modest results have limited their appeal.
+Added: Newer drugs, like GLP-1 receptor agonists (e.g., OzempicTM, WegovyTM), are quickly becoming the gold standard in the market.
+Added: These drugs, which mimic the action of gut hormones to promote satiety and reduce appetite, have shown remarkable efficacy in clinical trials and are significantly improving patient outcomes.
+Added: The success of GLP-1s has led to a surge in interest from both pharmaceutical companies and patients.
+Added: However, issues such as high cost, insurance reimbursement, and potential long-term side effects remain areas of concern.
+Added: The future of the obesity market is promising, with new therapies, enhanced patient targeting, and continued scientific breakthroughs on the horizon.
+Added: As the global obesity epidemic continues to grow, demand for more effective and affordable treatments will likely continue to rise.
+Added: However, success will depend on overcoming challenges related to cost, access, and patient adherence.
+Added: Advancements in personalized medicine, non-invasive treatments, and innovative drug mechanisms will shape the next phase of the obesity treatment landscape.
+Added: The obesity market today is vibrant and expanding, but still in need of accessible, scalable, and sustainable solutions to effectively manage this complex and widespread health issue.
+Added: We were historically involved in developing adoptive T-cell receptor, or TCR, engineered T-cell therapies, or TCR-T, designed to treat multiple solid tumor types in large cancer patient populations with unmet clinical needs.
We leveraged our cancer hotspot mutation TCR library and our proprietary, non-viral Sleeping Beauty gene transfer platform to design and manufacture patient-specific cell therapies that target neoantigens arising from common tumor-related mutations in key oncogenic genes, including KRAS, TP53 and EGFR.
In collaboration with The University of Texas MD Anderson Cancer Center, or MD Anderson, we were enrolling and treating patients for a Phase 1/2 clinical trial evaluating 12 TCRs reactive to mutated KRAS, TP53 and EGFR from our TCR library for the investigational treatment of non-small cell lung, colorectal, endometrial, pancreatic, ovarian and bile duct cancers, which we refer to as our TCR-T Library Phase 1/2 Trial.
+Added: More information regarding our TCR-T clinical trial, strategy and approved is detailed on our 2023 Form 10-K.
+Added: Despite the encouraging TCR-T Library Phase 1/2 Trial data, based on the substantial cost to continue development and the current financing environment, we announced in August 2023 that we would not pursue any further development of our TCR-T clinical programs.
On August 14, 2023, the Company announced a strategic reprioritization of its business and wind down of its TCR-T Library Phase 1/2 Trial.
−Removed: In connection with the reprioritization, the Company has reduced its workforce by approximately 95% to date and continues working to reduce costs in order to extend its cash runway.
+Added: We are currently working to close the TCR-T clinical trial internally and externally with the Federal Drug Administration or FDA.
The Company continues to explore strategic alternatives, including, but not limited to, an acquisition, merger, reverse merger, sale of assets, strategic partnerships, capital raises or other transactions.
−Removed: The Company has engaged Cantor Fitzgerald & Co., or Cantor, to act as strategic advisor for this process.
−Removed: Separately, the Company is evaluating several potential in-licensing opportunities in obesity, oncology and virology.
−Removed: In addition, on August 14, 2023, we announced that we had provided the requisite notice to the National Cancer Institute, or NCI, to terminate the Cooperative Research and Development Agreement, dated January 9, 2017, by and among us, the NCI and Intrexon Corporation, or Intrexon, as amended (such agreement referred to herein as the CRADA), pursuant to its terms, effective October 13, 2023.
−Removed: Eight patients were treated and evaluated in our TCR-T Library Phase 1/2 Trial with three unique TCRs from our library, which targeted KRAS-G12D, TP5304175H, and KRAS-G12V hotspot mutations.
−Removed: Patients with pancreatic (3), colorectal (4) and non-small cell lung cancer (1) were treated, with certain pancreatic and colorectal patients also having lung metastases.
−Removed: Overall, the trial showed our T-cells were generally well-tolerated in all evaluable participants with no dose-limiting toxicities (DLTs) and no immune effector cell-associated neurotoxicity syndrome (ICANS) were observed.
−Removed: All cytokine release syndrome (CRS) events were within grades 1-3 and were self-limiting or resolved with standard clinical management and, in some cases, a single dose of tocilizumab.
−Removed: One patient with non-small cell lung cancer (NSCLC) achieved an objective partial response with six months progression-free survival.
−Removed: Six other patients achieved a best overall response of stable disease.
−Removed: The total overall response rate was 13% and disease control rate was 87% in evaluable patients with advanced, metastatic, refractory solid tumors (see Figure A).
−Removed: Disease control was measured by objective responses and stable disease.
−Removed: Increased secretion of interferon-gamma relative to baseline was detected in all patients' serum post-cell transfer suggesting recognition of the tumor by the infused TCR-T cells.
−Removed: Persistence of TCR-T cells in peripheral blood was detected in all evaluable patients at their last follow-up, including up to six months in one patient.
−Removed: Infiltration of TCR-T cells into the tumor was also detected in three samples where a fresh biopsy was collected suggesting homing to the tumor microenvironment.
−Removed: All patients have progressed or withdrawn from the trial and long-term follow-up is ongoing for a subset of patients with no further intervention per the treatment protocol.
−Removed: This trial established proof-of-concept that Sleeping Beauty TCR-T cells can result in objective clinical responses and recognize established tumors in vivo.
−Removed: Despite the encouraging TCR-T Library Phase 1/2 Trial data, based on the substantial cost to continue development and the current financing environment, we announced in August 2023 that we would not pursue any further development of our clinical programs.
−Removed: In the United States, solid tumors represent approximately 90% of new cancer diagnoses.
−Removed: Approximately 2.0 million people are expected to be diagnosed with cancer in the United States in 2023 and approximately 610,000 people are expected to die from cancer in the United States in 2023.
−Removed: Some of the cancers we targeted in our TCR-T Library Phase 1/2 Trial are expected to be among the most prevalent cancers diagnosed in the United States in 2023.
−Removed: In 2023, it was estimated that 238,340 people were expected to be diagnosed with lung and bronchus cancer, 153,020 were expected to be diagnosed with colorectal cancer, 66,200 people were expected to be diagnosed with endometrial cancer, 64,050 people were expected to be diagnosed with pancreatic cancer, 19,710 people were expected be diagnosed with ovarian cancer and approximately 8,000 people were expected to be diagnosed with bile duct cancer.
−Removed: Mutations of the KRAS , TP53 and EGFR genes are commonly expressed across a wide variety of cancers.
−Removed: Our TCR-T Library Phase 1/2 Trial Approach
−Removed: The table below sets forth our multiple solid tumor pipeline programs.
−Removed: Our TCR-T program targeting solid tumors consisted of:
−Removed: • TCR Library :
−Removed: We built a TCR library that targets shared hotspot mutations known to be one of the key causes of cancer.
−Removed: These are non-inherited mutations.
−Removed: We in-licensed from the NCI multiple TCRs derived from third parties that are reactive to mutated KRAS , TP53 and EGFR .
−Removed: • Sleeping Beauty Gene Transfer Platform :
−Removed: Our proprietary non-viral genetic engineering technology utilizes a particular enzyme referred to as a transposase to cut and paste donor DNA referred to as a transposon into chromosomes of a T cell using a process called transposition.
−Removed: • hunTR ® ( hu man n eoantigen T cell R eceptor) Discovery Engine :
−Removed: Our robust and innovative TCR discovery engine enabled us to rapidly identify new TCRs to add to the TCR library.
−Removed: Using our hunTR discovery engine, we were able to analyze thousands of single T cells simultaneously using state-of-the-art bioinformatics and next generation sequencing.
−Removed: We aimed to maximize the breadth of our TCR library by evaluating both helper (CD4) and killer (CD8) T cells.
−Removed: We believe our TCR-T program has several potential advantages over other cell therapy approaches for solid tumors, including CAR-T and tumor-infiltrating lymphocytes, or TIL.
−Removed: As compared to CAR-T, these potential advantages include that our TCR-T program targeted intracellular and extracellular neoantigens whereas CAR-T primarily targets extracellular antigens.
−Removed: As compared to TIL, these potential advantages include that our TCR-T program defined target specificity from the genetic engineering employed in manufacturing whereas in TIL specificity typically arises from the endogenous TCR rather than an introduced immunoreceptor.
−Removed: Background on TCRs
−Removed: Our strategy was to target the hallmark of genomic instability in cancer with TCRs.
−Removed: Genes in cancer cells can lead to the production of proteins, which are then processed by the cell into protein fragments known as peptides.
−Removed: These peptides are presented to T cells by a specialized set of molecules on the cancer cell surface called the human leukocyte antigen, or HLA, system.
−Removed: When peptide presentation occurs, and it results in T cell activation through the TCR, the peptides are known as antigens.
−Removed: When these immunogenic peptides are derived from proteins which are in turn expressed from genes that are mutated only in tumor cells (for example, within the cancer genome and not encoded in the germline), they are known as neoantigens.
−Removed: Tumor cells presenting neoantigens via
−Removed: HLA are targets for T cells.
−Removed: T cells can recognize and kill neoantigen-presenting cancer cells.
−Removed: This approach is different from traditional CARs, which directly recognize antigens, such as CD19, on the surface of malignant B cells, without presentation by HLA.
−Removed: In general, the immune system avoids targeting the body’s own healthy cells principally through processes known as immune tolerance by which T cells do not respond to HLA containing peptides from normal proteins.
−Removed: The recognition by the TCR of a peptide presented by the HLA system is a vital immune mechanism that allows the body both to respond against foreign threats, including cancer, as well as to avoid targeting the body’s own healthy cells.
−Removed: Tumors utilize a variety of strategies to evade and suppress the host immune system.
−Removed: This often renders T cells residing within the tumor, referred to as TILs, ineffective and, despite expressing tumor-specific TCRs, unable to recycle their effector functions to kill tumors.
−Removed: To overcome immune suppression, healthier T cells are likely needed, such as those found in the peripheral blood.
−Removed: However, these circulating T cells do not typically express tumor-specific TCRs in adequate numbers.
−Removed: Neoantigens are encoded by tumor-specific mutated genes that are often unique to each patient.
−Removed: Targeting these unique neoantigens requires TCRs that are generated on a patient-by-patient basis.
−Removed: During cancer initiation and progression, tumor cells acquire mutations in naturally occurring genes that are responsible for transformation, known as driver mutations.
−Removed: Some of these driver mutations occur in common places called hotspots and are a class of mutations shared between tumor types and between individuals.
−Removed: Since driver mutations can be anticipated, it is possible to prepare TCRs in advance of a patient’s need and form a library of banked TCRs.
−Removed: Our Approach to Targeting Neoantigens
−Removed: We believe that to be successful in treating solid tumors, genetically modified T cells targeting one or more neoantigens will likely need to address the fact that (1) among a population of patients, not all tumors express the targeted neoantigen, referred to as inter-tumor heterogeneity, and (2) within a single patient, not all tumor cells express the targeted antigen, referred to as intra-tumor heterogeneity.
−Removed: Inter-tumor heterogeneity limits the number of recipients that are eligible to receive a treatment and intra-tumor heterogeneity creates the risk of antigen-escape variants, increasing the likelihood of cancer relapse.
−Removed: As a result, we believe companies developing T cell therapies targeting neoantigens must address both inter- and intra-tumor heterogeneity.
−Removed: We genetically modified peripheral blood-derived T cells to express TCRs with specificity to tumor-derived antigens, especially neoantigens, and propagated them to sufficient numbers prior to administration.
−Removed: We aimed to overcome the key challenges of targeting neoantigens by using DNA plasmids to reprogram T cells to express introduced TCRs on a patient-by-patient basis.
−Removed: This was designed to help address tumor heterogeneity.
−Removed: Our TCR-T cells contained multiple different subsets of T cells, including effector and memory T cells.
−Removed: The effector T cells were associated with immediate anti-tumor activity.
−Removed: Memory T cells have greater growth potential relative to the effector T cells.
−Removed: Some of our TCR-T cells were T memory stem cells, which have been described to have the largest capacity for growth and renewal relative to other T-cell populations.
−Removed: Our TCR-T Manufacturing Process
−Removed: The diagram below illustrates our manufacturing process for our TCR-T product candidates.
−Removed: Our TCR-T approach focused on what we believed to be the most critical and prevalent tumor-specific targets in cancer.
−Removed: These target mutations, called hotspots, are prevalent in genes including KRAS, TP53 and EGFR, which can be found in non-small cell lung, colorectal, endometrial, pancreatic, ovarian and bile duct cancers in several different HLA alleles.
−Removed: These driver genes play a key role in regulating cell division, maturation and death, and mutations in these genes have been observed to play a critical role in the development of certain cancers.
−Removed: The advantage of our Library TCR-T approach was that subsets of patients with solid tumors could potentially be rapidly treated by screening them for targeted neoantigens (e.g., KRAS , TP53 and EGFR ), identifying patient HLA, and matching these results to the TCRs in the library.
−Removed: Patients with a variety of different cancers (e.g., non-small cell lung, colorectal, endometrial, pancreatic, ovarian and bile duct cancers) could be screened for a match to our TCR library through tumor sequencing and identification of the patient’s tumor mutation and HLA typing.
−Removed: Once a match to our TCR library was confirmed, a portion of the patient’s white blood cells was collected through a peripheral blood leukapheresis and sent to our in-house current Good Manufacturing Practices, or cGMP, manufacturing facility in Houston, Texas.
−Removed: Once the desired pre-manufactured TCR transposon was selected from our TCR library, we utilized our proprietary non-viral Sleeping Beauty genetic engineering technology to modify the patient’s T cells (both CD4+ and CD8+).
−Removed: We used T cells from peripheral blood, which have a younger and healthier phenotype relative to tumor-resident T cells, to generate our TCR-T cells.
−Removed: Given initial clinical cellular kinetics of the TCR-T cells in the patients treated to date, we believed these modified TCR-T cells would persist in the recipient following infusion.
−Removed: We observed in preclinical studies that genetic engineering of T cells by our Sleeping Beauty technology resulted in the rapid and stable expression of the introduced neoantigen-specific TCR.
−Removed: The genetically modified T cells expressing high levels of the TCR were expanded to produce the patient-specific, or autologous, TCR-T cell product.
−Removed: The product candidate was then harvested from the manufacturing process, formulated, cryopreserved, transferred to the hospital facility and infused in the patient after thawing.
−Removed: Benefits of Our Non-Viral Sleeping Beauty Gene Transfer Platform
−Removed: Our Sleeping Beauty gene transfer platform provides several benefits, including those described below.
−Removed: • Scalability and Reduction in Complexity .
−Removed: The Sleeping Beauty technology is a straightforward means to manufacture a large number of autologous T-cell products.
−Removed: The technology requires only the synthesis of DNA plasmids as the starting material for genetic engineering of the T cells.
−Removed: In contrast, traditional viral gene transfer is more complex and requires specialized manufacturing of each viral vector(s) of interest.
−Removed: Production of a viral vector starts with the generation of plasmid DNA with the transgene of interest.
−Removed: This plasmid is then introduced into a packaging cell line and viruses are secreted into the media over a couple of days.
−Removed: This process is inherently more complex to scale with the numbers of cells and associated media required relative to Sleeping Beauty, which only requires the plasmid DNA.
−Removed: Genetic modification of the patient cells using the Sleeping Beauty technology is accomplished through electroporation with the DNA plasmids and subsequent culture, selection and growth of the T cells to large numbers using traditional manufacturing techniques.
−Removed: This simple process can be scaled through the addition of manufacturing lines.
−Removed: • Customizable Therapies .
−Removed: We believe our Sleeping Beauty platform provided us with the ability to manufacture more customizable therapies.
−Removed: The platform enabled a library of TCRs to be assembled and used in cells to recognize diverse mutations within shared
−Removed: neoantigens and address a multitude of HLA types.
−Removed: We believe this could enable both our Library TCR-T approach against shared cancer targets as well as personalized TCR therapies against unique, and potentially multiple, personal neoantigens.
−Removed: We believe multiplexing TCR-T cells, which involves infusing a patient with more than one TCR product, would be best enabled by our Sleeping Beauty system and through our unique TCRs and expanding TCR library.
−Removed: • Potential Clinical Benefits .
−Removed: We believe the anti-tumor activity of our TCR-T cells have the potential to last as long as the TCR-T cells persist and proliferate following the recognition of the neoantigen on the tumor cell surface.
−Removed: This may lead to durable and progressively greater clinical response in patients.
−Removed: In CAR-T cell products generated in human cells, Sleeping Beauty transposons were observed to integrate in a close-to-random distribution at thymine-adenine, or TA, dinucleotide sites, which increases the likelihood of insertion in a genomic safe harbor, thereby making them less likely to cause off-target effects when compared to other transposons and viral gene delivery methods.
−Removed: We also believe that including membrane-bound interleukin-15, or mbIL-15, in TCR-T cells can provide additional benefits.
−Removed: In particular, we have observed that T cells modified to express mbIL-15 as well as a TCR show increased potential for stemness corresponding with a potential ability to persist longer in the patient after infusion.
−Removed: • Accommodation of Large Transgene Size .
−Removed: Plasmids manufactured using our Sleeping Beauty platform have a large enough payload size to allow for genetic engineering of both the TCR as well as insertion of a gene encoding for the expression of cytokines, such as mbIL-15.
−Removed: This facilitates uniformly high co-expression of both the TCR and cytokine on a single integrated gene.
Preclinical and Clinical Development
−Removed: Preclinical Development of our TCR-T Product Candidates
−Removed: We independently evaluated all the TCRs we had licensed from NCI using our Sleeping Beauty platform.
−Removed: Candidate TCRs for clinical translation were selected based on conventional in vitro immunological measurements.
−Removed: We presented these data at the 2021 American Association for Cancer Research (AACR) and Society for Immunotherapy of Cancer (SITC) annual meetings.
−Removed: We selected the TCRs based, in part, on their ability to express on the T cell surface and then specifically recognize the mutated target without also targeting healthy cells.
−Removed: For those TCRs that are destined for killer T cells, our preclinical data suggested that those TCR-T cells could kill the appropriate tumor cell lines expressing the target neoantigen.
−Removed: In our preclinical studies, we also observed TCR-T cells killed significantly more tumor cells when matched with the corresponding HLA and neoantigen relative to mismatched tumor cells and relative to mismatched T cells not expressing the relevant neoantigen-specific TCR.
−Removed: Selected formerly licensed TCRs were co-expressed with mbIL-15 on T cells.
−Removed: This was accomplished with the transfer of a single transposon to deliver three independent genes (TCRalpha, TCRbeta, mbIL-15) to the T cell.
−Removed: We optimized the orientation order of these three genes and the growth conditions specific for the generation of mbIL-15 TCR-T cells.
−Removed: Using similar standard immunologic readouts described above, the mbIL-15 TCR-T cells were observed to display a similar specificity and potency profile to conventional TCR-T cells;
−Removed: however, we observed increased in vitro survival of mbIL-15 TCR-T cells in the absence of all added support relative to TCR-T cells, especially in the T memory stem cell populations.
−Removed: We filed an international patent application around these findings and presented preclinical data from this program at the American Society of Gene & Cell Therapy conference in 2022.
−Removed: We believe mbIL-15 has the potential to increase the survival of TCR-T cells in the harsh tumor microenvironment and deepen clinical responses.
−Removed: TCR-T Library Phase 1/2 Trial
−Removed: In February 2021, we received FDA clearance for our company-sponsored IND to initiate a Phase 1/2 open-label, dose-escalation trial which was initially being conducted at MD Anderson.
−Removed: In January 2022, after screening patients, we opened enrollment in our TCR-T Library Phase 1/2 Trial and expected to enroll up to 180 adults during the course of the trial.
−Removed: We only enrolled patients who had a matched HLA and hotspot mutation that was targeted by one of the TCRs from our TCR library, who had progressive or recurrent solid tumors and who had failed at least one prior line of standard therapy.
−Removed: The trial was evaluating the 12 TCRs that were in our library that targeted neoantigens arising from KRAS , TP53 and EGFR mutations in patients across a broad range of solid tumors that include non-small cell lung, colorectal, endometrial, pancreatic, ovarian, and bile duct cancers, all in a single trial.
−Removed: We intended to use our hunTR discovery engine in an effort to add new TCRs to the library and clinical program as they were qualified by our laboratory.
−Removed: The patients were enrolled in cohorts according to their cancer at three separate dose levels.
−Removed: The Phase 1 primary endpoint was to define dose limiting toxicity or the recommended maximum tolerated dose for a subsequent clinical trial.
−Removed: The primary endpoints for the Phase 2 portion of the trial was expected to determine the objective response rate and otherwise evaluate safety and tolerability.
−Removed: We were also monitoring TCR-T cell persistence and performing multiple conventional immune monitoring assays in the clinical trial to evaluate their persistence in patients.
−Removed: As of December 31, 2023, we have enrolled and dosed 8 patients.
−Removed: We presented information on the first two patients treated in September 2022 at the CRI-ENCI-AACR International Cancer Immunotherapy Conference, or CICON.
−Removed: The first patient we treated had lung adenocarcinoma with multiple lines of prior therapy and was refractory to checkpoint inhibitors.
−Removed: The second patient we treated was diagnosed with colon cancer and had received multiple lines of standard prior therapies.
−Removed: We successfully dosed a third patient who was diagnosed with advanced pancreatic cancer refractory to multiple lines of standard therapy in our TCR-T Library Phase 1/2 Trial in December 2022.
−Removed: We performed translational assessments to assess the biological activity of our TCR-T cells in order to guide next generation TCR-T therapy approaches including potential combination and multiplexed TCR-T cell
−Removed: We believe that these data provided early clinical validation of the potential of Sleeping Beauty TCR-T cell therapy in high value indications with significant unmet need.
−Removed: • All patients treated demonstrated manageable safety profiles with no dose limiting toxicities, or DLTs, or immune effector cell-associated neurotoxicity syndrome;
−Removed: • Persistence of the TCR-T cells has been observed.
−Removed: Patient 1 had persistence at 24 weeks with approximately 30% of the patient's total CD3+ T cells comprising TCR-T cells in peripheral blood after treatment with KRAS-G12D/HLA-A*11:01 mutation-specific TCR-T cells at dose level 1 (9x10 9 cells).
−Removed: Patient 2 had persistence at 12 weeks with approximately 20% of the patient's total CD3+ T cells comprising TCR-T cells in peripheral blood after treatment with TP53-R175H/HLA-A*02:01 mutation-specific TCR-T cells at dose level 2 (64x10 9 cells).
−Removed: • Demonstrating six month progression-free survival, Patient 1 had a best overall response of objective, partial response with regression of greater than 50% of target lesions at 12 weeks post-cell therapy.
−Removed: Patient 2 had a best overall response of stable disease at six weeks with 12 week progression-free survival.
−Removed: Progressive disease was observed in Patient 1 and Patient 2 at weeks 24 and 12, respectively, and each patient subsequently went off study;
−Removed: • The targeted mutations, KRAS-G12D and TP53-R175H, were detected in respective progressing tumor biopsies suggesting no antigen loss;
−Removed: • Tumor homing was observed in Patient 1 with infiltration of both CD4 and CD8 TCR-T cells six months post-TCR-T cell therapy.
−Removed: To our knowledge, achievement of an objective clinical response resulting from treatment with KRAS-G12D and HLA-A*11:01 specific TCR-T cells had not been reported until Patient 1 in our TCR-T Library Phase 1/2 Trial.
−Removed: Patient 1’s infusion product was high quality with 97.3% viability, 99.7% CD3+ purity and 95.2% TCR positivity.
−Removed: Patient 1’s target lesions were reduced compared to baseline by 46% at six weeks, 51% at 12 weeks and 46% at 24 weeks.
−Removed: At six months following treatment, an elective tumor biopsy of non-measurable disease in the right lung showed continued presence of tumor cells, KRAS-G12D mutation and HLA-A*11:01 allele, and progressive disease was corroborated by another elective scan at seven months.
−Removed: Patient 1 is now off trial and is being monitored as part of our long-term follow-up protocol.
−Removed: Patient 2's treatment was the first-in-human Sleeping Beauty TCR-T cell therapy targeting TP53 hotspot mutations and was generally well tolerated.
−Removed: The same TCR used by the NCI to treat breast cancer, which resulted in a 6-month confirmed, objective partial response, was used to treat Patient 2.
−Removed: Patient 2 received highly pure TCR-T cells (92.5% viability, 99% CD3+ purity, and 92% TCR positivity).
−Removed: Reduction of target lesions by 15% from baseline was observed at six weeks post-infusion, but we observed 21.8% growth of lesions from the week six measurements and appearance of new liver and lung metastases at week 12 signaled progressive disease in Patient 2, who was removed from the trial as a result of such progression.
−Removed: In the fourth quarter of 2022, we submitted an IND amendment to the FDA to add two new TCRs to our clinical trial targeting frequent mutations and HLAs, with the potential to double the addressable market of our TCR-T Library Phase 1/2 Trial.
−Removed: In over 700 patients screened at MD Anderson Cancer Center with gastrointestinal or lung tumors, we improved our match rate from 5% to over 10%, including roughly one in five patients matching two TCRs in the library.
−Removed: The addition of these new TCRs highlighted our strategy to add both more HLAs to existing mutations (KRAS-G12V and HLA-DRB1*07:01) and new mutations within our targeted gene families (TP53-R273C and HLA-DPB1*04:02).
−Removed: The IND amendment also combined our treatment and screening protocols, streamlining enrollment and potentially making it easier for both patients and physicians.
−Removed: The amended IND also eliminated the requirement for retesting of the tumor mutation if six months had passed between screening and treatment.
−Removed: Manufacturing
−Removed: In 2023, Our cGMP facility in Houston, Texas was staffed by Alaunos personnel and was fully operational for manufacturing TCR T-cells genetically modified with our Sleeping Beauty gene transfer platform for our early-stage clinical trials.
−Removed: We relied on third parties for the production of the DNA plasmids used in manufacturing our product candidates.
−Removed: We closed our cGMP facility in Houston in November 2023 and laid off all manufacturing personnel by September 2023.
−Removed: Our Library TCR-T approach allowed us to streamline the T cell manufacturing process by pre-manufacturing DNA plasmids corresponding to each of our qualified library TCRs.
−Removed: These TCRs were then utilized in the manufacturing for the patient-specific, autologous TCR-T product candidates.
−Removed: Our in-house TCR-T manufacturing facility also allowed us to integrate our research and development capabilities, potentially reducing the time from discovery to treating patients in a clinical trial.
−Removed: This integration was designed to minimize delays and reduce risks that can be encountered in drug development, including the failure of third parties to successfully produce the desired product, long technology transfer periods and long lead times for orders.
−Removed: We doubled our manufacturing capacity in 2022, allowing for production of two products simultaneously.
−Removed: We also filed an IND amendment to move from fresh to cryopreserved product and began implementing this change in the first half of 2023.
−Removed: The use of cryopreserved cell products was expected to reduce manufacturing process time from 30 days to 26 days, a 13% decrease, while increasing flexibility for patient scheduling and treatment.
−Removed: IL-12 Program
−Removed: As we announced in May 2021, we are winding down our existing Controlled IL-12 clinical program for the treatment of recurrent glioblastoma multiforme.
−Removed: On April 4, 2023, we returned the IL-12 assets to Precigen, Inc.
−Removed: via the parties' Amended and Restated Exclusive License Agreement.
+Added: Preclinical Development of our Obesity Product Candidates
+Added: We aim to develop an oral obesity compound that addresses many of the shortcomings of injectable GLP-1 receptor agonists including preserving lean muscle mass.
+Added: The ongoing in vitro study aims to evaluate the impact of ALN1001 and its derivatives on lipid deposition and gene expression.
+Added: This study evaluates if genes related to thermogenic activity, lipid metabolism, and energy regulation are activated or deactivated by treatment, to determine if these compounds positively affect fat and energy metabolism.
+Added: The results of this study, which are expected early second quarter of 2025, will provide critical insights into the development strategy for ALN1001 and its derivatives for obesity, metabolic disorders, and inflammation.
+Added: Drug development candidates most effective in increasing metabolic activity and reducing fat accumulation may be advanced to evaluation of the compounds in rodent models of obesity.
+Added: As is standard in the industry, if the aforementioned in vitro study is successful, we plan to conduct a proof-of-concept diet-induced obesity or DIO mouse study to validate our mechanism of action by the third quarter of 2025 before proceeding to Investigational New Drug or IND Application enabling studies.
+Added: Our ability to execute on this plan is dependent on study results and our ability to raise additional capital or partner these assets with other companies or research institutions.
+Added: Manufacturing of our Obesity Product Candidates
+Added: We currently outsource the manufacturing of our active pharmaceutical ingredient or API to a third party vendor with extensive experience in manufacturing small molecule drug products.
Intellectual Property
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Our policy is to actively seek the strongest possible intellectual property protection for our technology and product candidates through a combination of license agreements and owned patents, both in the United States and abroad.
−Removed: Owned Patents
+Added: Alaunos Patents & Patent Applications
As of December 31, 2024, we have six families of pending patent applications that cover our TCR-T library, products and processes.
6 unchanged sentences
The submission date of a New Drug Application, or NDA, plus the period of time between the submission date of the NDA or the issue date of the patent, whichever is later, and FDA approval.
−Removed: The United States Patent and Trademark Office, or USPTO, in consultation with the FDA, reviews and approves applications for any patent term extension or restoration.
+Added: The United States Patent
+Added: and Trademark Office, or USPTO, in consultation with the FDA, reviews and approves applications for any patent term extension or restoration.
We intend to seek the benefits of this statute, but there can be no assurance that we will be able to obtain any such benefits.
6 unchanged sentences
License Agreements
−Removed: Exclusive License Agreement with PGEN Therapeutics
−Removed: On October 5, 2018, we entered into an exclusive license agreement, or License Agreement, with PGEN Therapeutics, or PGEN, a wholly owned subsidiary of Precigen Inc., or Precigen, which was formerly known as Intrexon Corporation.
−Removed: Pursuant to the terms of the License Agreement, we had exclusive, worldwide rights to research, develop and commercialize (i) TCR products designed for neoantigens for the treatment of cancer, (ii) products utilizing Precigen’s RheoSwitch® gene switch, or RTS, for the treatment of cancer, referred to as IL-12 Products and (iii) CAR products directed to (A) CD19 for the treatment of cancer, referred to as CD19 Products, and (B) BCMA for the treatment of cancer, subject to certain obligations to pursue such target under the License and Collaboration Agreement effective March 27, 2015 between us, Precigen and ARES TRADING S.A., a subsidiary of Merck KGaA, as assigned by Precigen to PGEN.
−Removed: Under the License Agreement, we also have exclusive, worldwide rights for certain patents relating to the Sleeping Beauty technology to research, develop and commercialize TCR products for both neoantigens and shared antigens for the treatment of cancer, referred to as TCR Products.
−Removed: We were solely responsible for all aspects of the research, development and commercialization of the exclusively licensed products for the treatment of cancer as well as required to use commercially reasonable efforts, as defined in the License Agreement, to develop and commercialize IL-12 products, CD19 products and TCR Products.
−Removed: The License Agreement required us to pay PGEN an annual license fee of $0.1 million and reimburse PGEN for certain historical costs of the licensed programs.
−Removed: We were required to make milestone payments totaling up to an additional $52.5 million for each exclusively licensed program upon the initiation of later stage clinical trials and upon the approval of exclusively licensed products in various jurisdictions and pay PGEN tiered royalties ranging from low-single digit to high-single digit on the net sales derived from the sales of any approved IL-12 products and CAR products.
−Removed: We were also to pay PGEN royalties ranging from low-single digit to mid-single digit on the net sales derived from the sales of any approved TCR products, up to a maximum royalty amount of
−Removed: $100.0 million in the aggregate, 0% of any sublicensing income received by us relating to the licensed products, and fund development costs associated with each of the licensed products.
−Removed: PGEN was required to pay us royalties ranging from low-single digits to mid-single digits on the net sales derived from the sale of PGEN’s CAR products, up to a maximum royalty amount of $100.0 million.
−Removed: In October 2020, we entered into an amendment to the License Agreement relating to the transfer of certain materials and PGEN’s obligations to provide transition assistance relating to the IL-12 products.
−Removed: In April 2023, we amended and restated the License Agreement by entering into the Amended and Restated License Agreement, or A&R License, which replaces in its entirety the License Agreement.
−Removed: We returned all rights to the CAR-T and IL-12 programs to Precigen.
−Removed: We were granted, royalty-free, an exclusive, worldwide, sublicensable rights to research, develop and commercialize TCR products designed for neoantigens for the treatment of cancer.
−Removed: We are required to pay Precigen a $75,000 annual license payment.
License Agreement and 2015 Research and Development Agreement-The University of Texas MD Anderson Cancer Center
−Removed: On January 13, 2015, we, together with Precigen, entered into that certain license agreement, or the MD Anderson License, with MD Anderson (which Precigen subsequently assigned to PGEN).
−Removed: Pursuant to the MD Anderson License, we, together with PGEN, hold an exclusive, worldwide license to certain technologies owned and licensed by MD Anderson including technologies relating to novel CAR T-cell therapies, non-viral gene transfer systems, genetic modification and/or propagation of immune cells and other cellular therapy approaches, Natural Killer, or NK Cells, and TCRs, arising from the laboratory of Laurence Cooper, M.D., Ph.D.
−Removed: Cooper served as our Chief Executive Officer from May 2015 until February 2021 and was formerly a tenured professor of pediatrics at MD Anderson.
−Removed: On August 17, 2015, the Company, Precigen and MD Anderson entered into the Research and Development Agreement, or the 2015 R&D Agreement, to formalize the scope and process for the transfer by MD Anderson, pursuant to the terms of the MD Anderson License, of certain existing research programs and related technology rights, as well as the terms and conditions for future collaborative research and development of new and ongoing research programs.
−Removed: The rights and obligations of Precigen under the 2015 R&D Agreement were assigned to us pursuant to the Fourth Amendment to the 2015 R&D Agreement which was entered into on September 19, 2019, or the Fourth Amendment, with an effective date of October 5, 2018.
−Removed: The activities under the 2015 R&D Agreement are directed by a joint steering committee comprised of two members from our company and one member from MD Anderson.
−Removed: As provided under the MD Anderson License, we provided funding for research and development activities in support of the research programs under the 2015 R&D Agreement for a period of three years and in an amount of no less than $15.0 million and no greater than $20.0 million per year.
−Removed: On November 14, 2017, we entered into an amendment to the 2015 R&D Agreement extending its term until April 15, 2021 and on October 22, 2019, we entered into another amendment to the 2015 R&D Agreement extending its term until December 31, 2026 and to allow cash resources on hand at MD Anderson under the 2015 R&D Agreement to be used for development costs under the 2019 Research and Development Agreement, or the 2019 R&D Agreement, which we entered into on October 22, 2019, with MD Anderson, pursuant to which we agreed to collaborate with respect to the TCR program.
−Removed: The term of the MD Anderson License expires on the last to occur of (a) the expiration of all patents licensed thereunder, or (b) the twentieth anniversary of the date of the MD Anderson License;
−Removed: provided, however, that following the expiration of the term of the MD Anderson License, we, together with Precigen, shall then have a fully-paid up, royalty free, perpetual, irrevocable and sublicensable license to use the licensed intellectual property thereunder.
−Removed: After ten years from the date of the MD Anderson License and subject to a 90-day cure period, MD Anderson will have the right to convert the MD Anderson License into a non-exclusive license if we and Precigen are not using commercially reasonable efforts to commercialize the licensed intellectual property on a case-by-case basis.
−Removed: After five years from the date of the MD Anderson License and subject to a 180-day cure period, MD Anderson will have the right to terminate the MD Anderson License with respect to specific technology(ies) funded by the government or subject to a third-party contract if we and Precigen are not meeting the diligence requirements in such funding agreement or contract, as applicable.
−Removed: MD Anderson may also terminate the agreement with written notice upon material breach by us and Precigen, if such breach has not been cured within 60 days of receiving such notice.
−Removed: In addition, the MD Anderson License will terminate upon the occurrence of certain insolvency events for both us and Precigen and may be terminated by the mutual written agreement of us, Precigen, and MD Anderson.
+Added: On January 13, 2015, we and Precigen (later assigned to PGEN) entered into the MD Anderson License, granting us an exclusive global license to technologies from MD Anderson, primarily related to CAR T-cell therapies, non-viral gene transfer, genetic modification of immune cells, NK cells, and TCRs, developed by Laurence Cooper, M.D., Ph.D., our CEO from May 2015 to February 2021.
+Added: On August 17, 2015, we, Precigen, and MD Anderson executed the 2015 R&D Agreement, establishing the scope and terms for transferring existing and future research programs and technologies.
+Added: Precigen's rights were later assigned to us effective October 5, 2018.
+Added: A joint steering committee, including two members from our company and one from MD Anderson, oversees activities under this agreement.
+Added: Under the MD Anderson License, we funded R&D activities for three years at $15-20 million annually.
+Added: Amendments to the 2015 R&D Agreement extended its term first to April 15, 2021, then to December 31, 2026, and allowed existing funds to support costs under the 2019 R&D Agreement, initiated on October 22, 2019, focusing on the TCR program.
+Added: The MD Anderson License term ends upon the later of the expiration of all licensed patents or the twentieth anniversary of the agreement.
+Added: Post-expiration, we retain a perpetual, royalty-free, sublicensable license.
+Added: MD Anderson may convert the license to non-exclusive after ten years if we fail commercial diligence, or terminate specific technologies after five years if diligence requirements tied to funding or third-party contracts aren't met, subject to specified cure periods.
+Added: MD Anderson can terminate upon uncured material breach or certain insolvency events and through mutual agreement
2019 Research and Development Agreement-The University of Texas MD Anderson Cancer Center
−Removed: Under the 2019 R&D Agreement, we and MD Anderson will, among other things, collaborate on programs to expand our TCR library and conduct clinical trials.
−Removed: The activities under the 2019 R&D Agreement are directed by a joint steering committee comprised of two members from our company and one member from MD Anderson.
−Removed: We will own all inventions and intellectual property developed under the 2019 R&D Agreement and we will retain all rights to all intellectual property, patentable or not, for oncology products manufactured using non-viral gene transfer technologies under the 2019 R&D Agreement, including our Sleeping Beauty technology.
−Removed: We have granted MD Anderson an exclusive license for such intellectual property to develop and commercialize autologous TCR products manufactured using viral gene transfer technologies, and any products outside the field of oncology and a non-exclusive license for allogenic TCR products manufactured using viral-based technologies.
+Added: Under the 2019 R&D Agreement, we were to, along with MD Anderson, among other things, collaborate on programs to expand our TCR library and conduct clinical trials of the same.
+Added: The activities under the 2019 R&D Agreement are directed by a joint steering committee comprised of two members from the Company and one member from MD Anderson.
+Added: The Company will own all inventions and intellectual property developed under the 2019 R&D Agreement and the Company will retain all rights to all intellectual property, patentable or not, for oncology products manufactured using non-viral gene transfer technologies under the 2019 R&D Agreement, including the Sleeping Beauty technology.
+Added: We granted MD Anderson an exclusive license for such intellectual property to develop and commercialize autologous TCR products manufactured using viral gene transfer technologies and any products outside the field of oncology and a non-exclusive license for allogenic TCR products manufactured using viral-based technologies.
Under the 2019 R&D Agreement, we agreed, beginning on January 1, 2021, to reimburse MD Anderson up to a total of $20.0 million for development costs under the 2019 R&D Agreement, after the funds from the 2015 R&D Agreement are exhausted.
−Removed: In addition, we will pay MD Anderson royalties on net sales of its TCR products at rates in the low single digits.
−Removed: We are required to make performance-based payments upon the successful completion of clinical and regulatory benchmarks relating to its TCR products.
+Added: In addition, we will pay MD Anderson royalties on net sales of its TCR products, if any.
+Added: We are required to make performance-based payments upon the successful completion of clinical and regulatory benchmarks relating to our TCR products.
The aggregate potential benchmark payments are $36.5 million, of which only $3.0 million will be due prior to the first marketing approval of our TCR products.
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The 2019 R&D Agreement also contains customary provisions related to indemnification obligations, confidentiality and other matters.
−Removed: In connection with the execution of the 2019 R&D Agreement, on October 22, 2019, we issued MD Anderson a warrant to purchase 3,333,333 shares of our common stock, which is referred to as the MD Anderson Warrant.
−Removed: The MD Anderson Warrant has an initial exercise price of $0.001 per share, expires on December 31, 2026 and vests in four parts upon the occurrence of certain clinical milestones.
+Added: In connection with the execution of the 2019 R&D Agreement, on October 22, 2019, we issued MD Anderson a warrant to purchase 22,222 shares of the Company's common stock, which is referred to as the MD Anderson Warrant.
+Added: The MD Anderson Warrant has an initial exercise price of $0.15 per share, expires on December 31, 2026, and vests upon the occurrence of certain clinical milestones.
As of December 31, 2024, the milestones have not been met.
−Removed: The MD Anderson Warrant and the shares of our common stock to be issued upon exercise of the MD Anderson Warrant have not been registered under the Securities Act of 1933, as amended, and may not be offered or sold in the United States absent registration or an applicable exemption from registration requirements.
−Removed: License Agreement with the NCI
−Removed: On May 28, 2019, we entered into a patent license agreement, or the Patent License, with the NCI.
−Removed: Pursuant to the Patent License, we hold an exclusive, worldwide license to certain intellectual property to develop and commercialize patient-derived (autologous), peripheral blood T-cell therapy products engineered by transposon-mediated gene transfer to express TCRs reactive to mutated KRAS , TP53 and EGFR neoantigens.
−Removed: In addition, pursuant to the Patent License, we hold an exclusive, worldwide license to certain intellectual property for manufacturing technologies to develop and commercialize autologous, peripheral blood T-cell therapy products engineered by non-viral gene transfer to express TCRs, as well as a non-exclusive, worldwide license to certain additional manufacturing technologies.
−Removed: On May 29, 2019, January 8, 2020, September 28, 2020, April 16, 2021, May 4, 2021, and August 13, 2021 we amended the Patent License to expand our TCR library to include additional TCRs reactive to mutated KRAS and TP53 neoantigens licensed from the NCI.
−Removed: The terms of the Patent License required us to pay the NCI minimum annual royalties in the amount of $0.3 million, which amount will be reduced to $0.1 million once the aggregate minimum annual royalties paid by us equals $1.5 million.
−Removed: We were also required to make performance-based payments upon successful completion of clinical and regulatory benchmarks relating to the licensed products.
−Removed: Of such payments, the aggregate potential benchmark payments were $4.3 million, of which aggregate payments of $3.0 million was due only after marketing approval in the United States or in Europe, Japan, Australia, China or India.
−Removed: The first benchmark payment of $0.1 million was paid in 2022 upon the initiation of our TCR-T Library Phase 1/2 Trial, which was a qualifying Phase 1 clinical trial under the terms of the Patent License.
−Removed: In addition, we were required to pay the NCI one-time benchmark payments following aggregate net sales of licensed products at certain aggregate net sales ranging from $250.0 million to $1.0 billion.
−Removed: The aggregate potential amount of these benchmark payments is $12.0 million.
−Removed: We must also pay the NCI royalties on net sales of products covered by the Patent License at rates in the low to mid-single digits depending upon the technology included in a licensed product.
−Removed: To the extent we enter into a sublicensing agreement relating to a licensed product, we are required to pay the NCI a percentage of all consideration received from a sublicensee, which percentage will decrease based on the stage of development of the licensed product at the time of the sublicense.
−Removed: The Patent License was to expire upon expiration of the last patent contained in the licensed patent rights, unless terminated earlier.
−Removed: The NCI could have terminated or modified the Patent License in the event of a material breach, including if we did not meet certain milestones by certain dates, or upon certain insolvency events that remained uncured following the date that was 90 days following written notice of such breach or insolvency event.
−Removed: We could have terminated the Patent License, or any portion thereof, in our sole discretion at any time upon 60 days’ written notice to the NCI.
−Removed: In addition, the NCI had the right to:
−Removed: (i) require us to sublicense the rights to the product candidates covered by the Patent License upon certain conditions, including if we are not reasonably satisfying required health and safety needs and (ii) terminate or modify the Patent License, including if we are not satisfying requirements for public use as specified by federal regulations.
−Removed: On October 27, 2023, we provided the requisite 60-days' notice to the NCI of our intention to terminate the Patent License, effective December 26, 2023.
−Removed: The Patent License subsequently was terminated on that date.
−Removed: Cooperative Research and Development Agreement with the NCI
−Removed: On January 9, 2017, we entered into a Cooperative Research and Development Agreement, or CRADA, with the NCI.
−Removed: The purpose of this collaboration was to advance a personalized TCR-T approach for the treatment of solid tumors.
−Removed: Using our Sleeping Beauty technology, the NCI
−Removed: would analyze a patient’s own cancer cells, identify their unique neoantigens and TCRs reactive against those neoantigens and then use our Sleeping Beauty technology to transpose one or more TCRs into T cells for re-infusion.
−Removed: Research conducted under the CRADA was at the direction of Steven A.
−Removed: Rosenberg, M.D., Ph.D., Chief of the Surgery Branch at the NCI, in collaboration with our researchers.
−Removed: We were responsible for providing the NCI with the test materials necessary for them to conduct their studies, and eventually, clinical trials pursuant to the CRADA.
−Removed: Inventions, data and materials discovered or produced in connection with performance of the research plan under the CRADA would have remained the sole property of the party who produced the discovery.
−Removed: The parties would have jointly owned all inventions jointly discovered under the research plan.
−Removed: The owner of any invention under the CRADA would have made the decision to file a patent covering the invention, or in the case of a jointly owned invention, we would have had the first opportunity to file a patent covering the invention.
−Removed: If we failed to provide timely notice of our decision to the NCI or decided not to file a patent covering the joint invention, NCI had the right to make the filing.
−Removed: For any invention solely owned by NCI or jointly made by NCI and us for which a patent application was filed, the U.S.
−Removed: Public Health service would have granted us an exclusive option to elect an exclusive or non-exclusive commercialization license.
−Removed: For inventions owned solely by NCI or jointly owned by NCI and us, which are licensed according to the terms described above, we agreed to grant to the U.S.
−Removed: government a non-exclusive, non-transferable, irrevocable and paid up license to practice the invention or have the invention practiced on its behalf throughout the world.
−Removed: We were also required to grant the U.S.
−Removed: government a non-exclusive, non-transferable, irrevocable and paid up license to practice the invention or have the invention practiced on its behalf throughout the world for any of our solely owned inventions.
−Removed: The agreement could have been terminated by any of the parties upon 60 days prior written consent.
−Removed: The NCI had a cleared IND that would permit them to begin this trial.
−Removed: To our knowledge, the trial has not yet enrolled.
−Removed: The progress and timeline for this trial, including the timeline for dosing patients, were under control of the NCI.
−Removed: In February 2019, we extended the CRADA with the NCI until January 9, 2022, committing an additional $5.0 million to this program.
−Removed: In March 2022, we entered into an amendment to the CRADA that is retroactive, effective January 9, 2022 to extend the term of the CRADA until January 9, 2023.
−Removed: In June 2022, we entered into the Fourth Amendment to the CRADA, or the CRADA Fourth Amendment, which, among other things, extended the term of the CRADA until January 9, 2025.
−Removed: In connection with the CRADA Fourth Amendment, we agreed to contribute $1.0 million per year, payable on a quarterly basis, beginning in the first quarter of 2023.
−Removed: On August 14, 2023, we provided the requisite 60-days' notice of our intention to terminate the CRADA, which did subsequently terminate at that time.
−Removed: TCR-T Platform Licenses
−Removed: In January 2015, we in-licensed from MD Anderson a technology portfolio that includes intellectual property directed to certain non-viral Sleeping Beauty technologies as well as TCR-T cell therapy and bioprocessing technology.
−Removed: Under the terms of the agreement, we have an exclusive license to certain of the intellectual property technology, a co-exclusive license to certain of the intellectual property technology and a non-exclusive license to certain of the intellectual property technology.
−Removed: Our rights to the MD Anderson intellectual property flow to us via our agreement with PGEN.
Governmental Regulation and Product Approval
−Removed: As a biopharmaceutical company, we are subject to extensive regulation.
−Removed: Our genetically engineered T-cell product candidates are regulated as biologics.
−Removed: With this classification, commercial production of our products will need to occur in registered and licensed facilities in compliance with cGMPs for biologics.
−Removed: Human immunotherapy products are a new category of therapeutics.
−Removed: The FDA categorizes human cell- or tissue-based products as either minimally manipulated or more than minimally manipulated and has determined that more than minimally manipulated products require clinical trials to demonstrate product safety and efficacy and the submission of a Biologics License Application, or BLA, for marketing authorization.
−Removed: Government authorities in the United States (at the federal, state and local level) and in other countries and jurisdictions extensively regulate, among other things, the research, development, preclinical and clinical testing, manufacturing, quality control, labeling, packaging, storage, record-keeping, promotion, advertising, sale, distribution, post-approval monitoring and reporting, marketing and export and import of biopharmaceutical products such as those we are developing.
+Added: Government authorities in the United States (at the federal, state and local level) and in other countries and jurisdictions extensively regulate, among other things, the research, development, preclinical and clinical testing, manufacturing, quality control, labeling, packaging, storage, record-keeping, promotion, advertising, sale, distribution, post-approval monitoring and reporting, marketing and export and import of pharmaceutical products such as those we are developing.
Our product candidates must be approved by the FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in foreign countries.
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Product Development Process
−Removed: In the United States, the FDA regulates biological products under the Public Health Service Act, or PHSA, and the Federal Food, Drug and Cosmetic Act, or FDCA, and implementing regulations.
+Added: In the United States, the FDA regulates pharmaceutical products under the Public Health Service Act, or PHSA, and the Federal Food, Drug and Cosmetic Act, or FDCA, and implementing regulations.
Products are also subject to other federal, state and local statutes and regulations.
−Removed: The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and
−Removed: regulations require the expenditure of substantial time and financial resources.
+Added: The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.
Failure to comply with the applicable United States requirements at any time during the product development process, approval process or after approval, may subject an applicant to administrative or judicial sanctions.
1 unchanged sentence
Any agency or judicial enforcement action could have a material adverse effect on us.
−Removed: The process required by the FDA before a biological product may be approved for marketing in the United States generally involves the following:
+Added: The process required by the FDA before a pharmaceutical product may be approved for marketing in the United States generally involves the following:
• completion of preclinical laboratory tests and animal studies according to Good Laboratory Practices, or GLPs, and applicable requirements for the humane use of laboratory animals or other applicable regulations;
1 unchanged sentence
• performance of adequate and well-controlled human clinical trials according to the FDA’s regulations commonly referred to as Good Clinical Practices, or GCPs, and any additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the proposed biological product for its intended use;
−Removed: • preparation and submission to the FDA of a BLA for marketing approval that includes substantive evidence of safety, purity and potency from results of nonclinical testing and clinical trials;
+Added: • preparation and submission to the FDA of an NDA or biologics license application or BLA for marketing approval that includes substantive evidence of safety, purity and potency from results of nonclinical testing and clinical trials;
• satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities where the biological product is produced to assess compliance with cGMP to assure that the facilities, methods and controls used in product manufacture are adequate to preserve the biological product’s identity, strength, quality and purity and, if applicable, the FDA’s current Good Tissue Practices, or GTPs, for the use of human cellular and tissue products;
−Removed: • potential FDA audit of the nonclinical study and clinical trial sites that generated the data in support of the BLA;
−Removed: • payment of user fees for FDA review of the BLA;
−Removed: • FDA acceptance, review and approval, or licensure, of the BLA, which might include review by an advisory committee, a panel typically consisting of independent clinicians and other experts who provide recommendations as to whether the application should be approved and under what conditions.
+Added: • potential FDA audit of the nonclinical study and clinical trial sites that generated the data in support of the NDA or BLA;
+Added: • payment of user fees for FDA review of the NDA or BLA;
+Added: • FDA acceptance, review and approval, or licensure, of the NDA or BLA, which might include review by an advisory committee, a panel typically consisting of independent clinicians and other experts who provide recommendations as to whether the application should be approved and under what conditions.
Before testing any biological product candidate, including our product candidates, in humans, the product candidate must undergo rigorous preclinical testing.
51 unchanged sentences
Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the BLA.
−Removed: The FDA reviews the BLA to determine, among other things, whether the proposed product
−Removed: is safe, potent, and/or effective for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, safety, strength, quality, potency and purity.
+Added: The FDA reviews the BLA to determine, among other things, whether the proposed product is safe, potent, and/or effective for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, safety, strength, quality, potency and purity.
The FDA may refer applications for novel biological products or biological products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.
30 unchanged sentences
The FDA also may require post-marketing testing, known as Phase 4 testing, and surveillance to monitor the effects of an approved product.
−Removed: Discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, with manufacturing processes, or the failure to comply with applicable FDA requirements can have negative consequences, including adverse
−Removed: publicity, judicial or administrative enforcement, complete withdrawal from the market, product recalls, warning letters from the FDA, mandated corrective advertising or communications with doctors, product seizure or detention, injunctions and civil or criminal penalties, among others.
+Added: Discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, with manufacturing processes, or the failure to comply with applicable FDA requirements can have negative consequences, including adverse publicity, judicial or administrative enforcement, complete withdrawal from the market, product recalls, warning letters from the FDA, mandated corrective advertising or communications with doctors, product seizure or detention, injunctions and civil or criminal penalties, among others.
Newly discovered or developed safety or effectiveness data may require changes to a product’s approved labeling, including the addition of new warnings and contraindications, and also may require the implementation of other risk management measures.
4 unchanged sentences
The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.
−Removed: Marketing Exclusivity
−Removed: The Biologics Price Competition and Innovation Act, or BPCIA, amended the PHSA to authorize the FDA to approve similar versions of innovative biologics, commonly known as biosimilars.
−Removed: Biosimilars are approved pursuant to an abbreviated pathway whereby applicants need not submit the full slate of preclinical and clinical data, and approval is based in part on the FDA’s findings of safety, purity, and potency for the original biologic (i.e., the reference product).
−Removed: Reference products are eligible to receive 12 years of exclusivity from the time of first licensure of the product, which prevents the FDA from approving any biosimilars to the reference product through the abbreviated pathway, but does not prevent approval of BLAs that are accompanied by a full data package and that do not rely on the reference product.
−Removed: A biosimilar may be approved if the product is highly similar to the reference product notwithstanding minor differences in clinically inactive components and there are no clinically meaningful differences with the reference product in terms of the safety, purity and potency.
−Removed: Pediatric exclusivity is another type of regulatory market exclusivity in the United States.
−Removed: Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms.
−Removed: This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial.
−Removed: Orphan Drug Designation
−Removed: Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the United States or, if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of developing and making a drug or biologic product available in the United States for this type of disease or condition will be recovered from sales of the product.
−Removed: Orphan designation must be requested before submitting a marketing application.
−Removed: After the FDA grants orphan designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.
−Removed: Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.
−Removed: If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same drug or biological product for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or inability to manufacture the product in sufficient quantities.
−Removed: The designation of such drug also entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user fee waivers.
−Removed: Competitors, however, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity.
−Removed: Orphan exclusivity also could block the approval of one of our products for seven years if a competitor obtains approval of the same product as defined by the FDA or if our product candidate is determined to be contained within the competitor’s product for the same indication or disease.
−Removed: If an orphan designated product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan exclusivity.
−Removed: Orphan drug status in the European Union, or EU, has similar but not identical benefits in that jurisdiction.
Coverage, Pricing and Reimbursement
5 unchanged sentences
In addition, in the United States, no uniform policy of coverage and reimbursement for drug products exists among third-party payors.
−Removed: Therefore, coverage and reimbursement for drug products can differ significantly from payor to
+Added: Therefore, coverage and reimbursement for drug products can differ significantly from payor to payor.
Third-party payors are increasingly challenging the price, examining the medical necessity of and reviewing the cost-effectiveness of medical products, therapies and services, in addition to questioning their safety and efficacy.
35 unchanged sentences
In March 2010, President Obama signed into law the ACA, which included measures that have significantly changed the way healthcare is financed by both governmental and private insurers.
−Removed: The ACA, among other things, imposed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program, extended the rebate program to individuals enrolled in Medicaid managed care organizations, added a provision to increase the Medicaid rebate for line extensions or reformulated drugs, established annual fees on manufacturers and importers of certain branded prescription drugs and biologic agents, promoted a new Medicare Part D coverage gap discount program, expanded the entities eligible for discounts under the Public Health Service Act pharmaceutical pricing program and imposed a number of substantial new compliance provisions related to pharmaceutical companies’ interactions with healthcare practitioners.
+Added: The ACA, among other things, imposed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program, extended the rebate program to individuals enrolled in Medicaid managed care organizations, added a provision to increase the Medicaid rebate for line extensions or
+Added: reformulated drugs, established annual fees on manufacturers and importers of certain branded prescription drugs and biologic agents, promoted a new Medicare Part D coverage gap discount program, expanded the entities eligible for discounts under the Public Health Service Act pharmaceutical pricing program and imposed a number of substantial new compliance provisions related to pharmaceutical companies’ interactions with healthcare practitioners.
The ACA also expanded eligibility for Medicaid programs and introduced a new Patient Centered Outcomes Research Institute to oversee, identify priorities in and conduct comparative clinical effectiveness research, along with funding for such research and a new Center for Medicare & Medicaid Innovation at CMS, to test innovative payment and service delivery models to lower Medicare and Medicaid spending.
2 unchanged sentences
Concurrently, Congress considered legislation to repeal or repeal and replace all or part of the ACA.
−Removed: While Congress has not passed repeal legislation, several bills affecting the implementation of certain taxes under the ACA have been signed into law.
+Added: While Congress has not passed legislation that would repeal the ACA in total, several bills affecting the implementation of certain taxes under the ACA have been signed into law.
The Tax Cuts and Jobs Act of 2017, or Tax Act, included a provision which repealed, effective January 1, 2019, the tax-based shared responsibility payment imposed by the ACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” Further, the 2020 federal spending package permanently eliminated, effective January 1, 2020, the ACA-mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1, 2021, also eliminated the health insurer tax.
−Removed: The Bipartisan Budget Act of 2018, or the BBA, among other things, amended the ACA, effective January 1, 2019, to increase from 50 percent to 70 percent the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole.” Further, President Biden issued an executive order that instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.
−Removed: Further, there have been a number of health reform initiatives by the Biden administration that have impacted the ACA.
−Removed: For example, on August 16, 2022, President Biden signed the Inflation Reduction Act, or IRA, into law, which, among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.
−Removed: The IRA also eliminates the "donut hole" under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and implementing a newly established manufacturer discount program.
−Removed: It is possible that the ACA will be subject to judicial or Congressional challenges in the future.
−Removed: It is unclear how any such challenges and the healthcare reform measures of the Biden administration will impact ACA and our business.
+Added: The Bipartisan Budget Act of 2018, or the BBA, among other things, amended the ACA, effective January 1, 2019, to increase from 50 percent to 70 percent the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole.” Further, President Biden had issued an executive order that instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA, though this and similar Biden-era policies are currently being revisited by the current Trump administration.
+Added: There had been a number of health reform initiatives by the Biden administration that have impacted the ACA, including adoption of the Inflation Reduction Act, or IRA, into law, which, among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.
+Added: The IRA also eliminated the "donut hole" under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and implementing a newly established manufacturer discount program.
+Added: It is possible that the ACA will be subject to judicial or Congressional challenges in the future, particularly in light of the Trump administration's interest in reducing federal expenditures to include those under federal healthcare programs..
+Added: It is unclear how any such challenges and the cost reduction measures of the Trump administration will impact ACA and our business.
The ultimate content, timing or effect of any healthcare reform measures on the U.S.
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For example, as a result of the Budget Control Act of 2011, providers are subject to Medicare payment reductions of 2% per fiscal year, which went into effect on April 1, 2013.
−Removed: This 2% reduction was temporarily suspended during the COVID-19 pandemic, but has since been reinstated and, unless Congress and/or the Executive Branch take additional action, will begin to increase gradually starting in April 2030, reaching 4% in April 2031, until sequestration ends in October 2031.
+Added: This 2% reduction was temporarily suspended during the COVID-19 pandemic, but has since been reinstated and, unless Congress and/or the Executive Branch take additional action will extend to 2032.
Further, the American Taxpayer Relief Act of 2012 reduced Medicare payments to several providers and increased the statute of limitations period for the government to recover overpayments from providers from three to five years.
6 unchanged sentences
The FDA also released a final rule, effective November 30, 2020, implementing a portion of the importation executive order providing guidance for states to build and submit importation plans for drugs from Canada.
−Removed: Further, on November 30, 2020, the U.S.
+Added: On November 30, 2020, the U.S.
Department of Health and Human Services, or HHS, finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.
2 unchanged sentences
the implementation of these provisions has also been delayed by the IRA until January 1, 2032.
−Removed: In addition, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate price cap, currently set at 100% of a drug’s average manufacturer price for single source and innovator multiple source products, beginning on January 1, 2024.
−Removed: Further, in July 2021, the Biden Administration released an executive order that included multiple provisions aimed at prescription drugs.
−Removed: In response to President Biden's executive order, on September 9, 2021, HHS released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug price reform.
−Removed: The plan sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions by HHS.
−Removed: No legislative or administrative actions have been finalized to implement these principles.
−Removed: In addition, Congress is considering drug pricing as part of the budget reconciliation process.
−Removed: Additionally, the IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, and subjects drug manufacturers to civil monetary penalties and a potential excise tax for offering a price that is not equal to or less than the negotiated “maximum fair price” under the law, and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.
+Added: In addition, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate price cap, which was set at 100% of a drug’s average manufacturer price for single source and innovator multiple source products, beginning on January 1, 2024.
+Added: The IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, and subjects drug manufacturers to civil monetary penalties and a potential excise tax for offering a price that is not equal to or less than the negotiated “maximum fair price” under the law, and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.
The IRA permits HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.
−Removed: These provisions began to take effect progressively starting in fiscal year 2023, although they may be subject to legal challenges.
+Added: These provisions began to take effect progressively starting
+Added: in fiscal year 2023, although they may be subject to legal challenges.
It is currently unclear how the IRA will be effectuated but is likely to have a significant impact on the pharmaceutical industry.
6 unchanged sentences
Activities that violate the FCPA, even if they occur wholly outside the United States, can result in criminal and civil fines, imprisonment, disgorgement, oversight, and debarment from government contracts.
−Removed: Our operations are also subject to non-United States anti-corruption laws such as the U.K.
−Removed: Bribery Act 2010, or the Bribery Act.
−Removed: As with the FCPA, these laws generally prohibit us and our employees and intermediaries from authorizing, promising, offering or providing, directly or indirectly, improper or prohibited payments, or anything else of value, to government officials or other persons to obtain or retain business or gain some other business advantage.
−Removed: Under the Bribery Act, we may also be liable for failing to prevent a person associated with us from committing a bribery offense.
−Removed: We are also subject to other laws and regulations governing our international operations, including regulations administered by the governments of the United Kingdom and the United States and authorities in the EU, including applicable export control regulations, economic sanctions and embargoes on certain countries and persons, anti-money laundering laws, import and customs requirements and currency exchange regulations, collectively referred to as trade control laws.
+Added: We are also subject to other laws and regulations governing our international operations, including regulations administered by the government of the United States, including applicable export control regulations, economic sanctions and embargoes on certain countries and persons, anti-money laundering laws, import and customs requirements and currency exchange regulations, collectively referred to as trade control laws.
Failure to comply with the Bribery Act, the FCPA and other anti-corruption laws and trade control laws could subject us to criminal and civil penalties, disgorgement and other sanctions and remedial measures, and legal expenses.
−Removed: We believe our novel hunTR discovery engine demonstrated the ability to identify proprietary TCRs, allowing us to further expand and advance our pipeline with multiple solid tumor programs under development.
+Added: We aim to develop an oral obesity compound that addresses many of the shortcomings of injectable GLP-1 receptor agonists including preserving lean muscle mass.
+Added: The goal of this program is to develop a drug with a differentiated profile relative to currently marketed and in development oral and injectable products.
+Added: We believe our small molecule product candidates are distinct in that they do not rely on hormonal manipulation, which is common with many other obesity treatments.
+Added: These treatments are currently being developed or marketed by many pharmaceutical or biotech companies at various stages.
+Added: While our small molecule product candidates are different from these competitors' product offerings, our goals are the same, to treat obesity, and therefore, we are competitors in the same market.
+Added: These competitors include 35 Pharma, Aardvark Tx, Altimmune, Amgen, Amplifier, Aphaia Pharma, Ascletis, AstraZeneca, Astrizi, BioAge Labs, Biomea Fusion, Biomed Industries, Boehringer Ingelheim, Clearmind, Corbus Pharma, Corxel, Currax Pharma, Eli Lilly, Empros Pharma, EndevicaBio, Entera/Opko, Epitomee, ERX Pharma, Gan & Lee Pharmaceuticals, Gilead, Glaceum, Glyscend, Halia Therapeutics, Hansoh Pharmaceutical, Huadong Medicine, Kailera/Hengrui, Kallyope, Lexicon, Merck, Metsera, Mindrank AI, Neurogastrx, NodThera, Novo Nordisk, OrsoBio, Pelagos, Pep2Tango Therapeutics, Pfizer, ProGen/Rani Therapeutics, Regeneron, Regor, Response Pharmaceuticals, Roche, Scilex, Scohia Pharma, Shionogi, Structure Tx, Syntis Bio, Terns Pharma, Verdiva Bio/Sciwind, Verge Genomics, Veru, and Viking Therapeutics.
+Added: We also believe our novel hunTR discovery engine demonstrated the ability to identify proprietary TCRs, allowing us to further expand and advance our pipeline with multiple solid tumor programs under development.
In addition, our non-viral transposon method of expressing TCRs, Sleeping Beauty, was less complex relative to many of our competitors’ viral approaches.
2 unchanged sentences
Many of these companies have more experience in preclinical and clinical development, manufacturing, regulatory, and global commercialization.
−Removed: Given the rapidly advancing and changing science and technologies in the industry, they may compete with us in hiring personnel, setting up clinical study sites, recruiting patients for clinical trials, and procuring technologies and licenses complementary to, or required for, our programs.
−Removed: We are also competing with academic institutions, governmental agencies and private organizations that are conducting research in the field of cancer.
−Removed: Our TCR-T cell therapies targeting solid tumors face significant competition from multiple companies, and their collaborators, in the TCR and CAR technology space.
−Removed: We face competition from several companies, including 2Seventy Bio, Achilles Therapeutics, Adaptimmune Therapeutics, Affini-T Therapeutics, Annoca, ArsenalBio, Athenex, BioNTech, Bristol-Myers Squibb, Immatics, Iovance Biotherapeutics, Kite (a Gilead company), Lion TCR, Lyell Immunopharma, Medigene, Nurix Therapeutics, Neogene Therapeutics (a member of the AstraZeneca group), NexImmune, PACT Pharma, Precigen, Tactiva Therapeutics, Takara Bio, TCR 2 Therapeutics, T-Cure BioScience, T-knife Therapeutics, Triumvira Immunologics, TScan Therapeutics, Turnstone Biologics, Zelluna Immunotherapy and others.
−Removed: Many of these companies are either investigating TCR-T cells against germline antigens or are utilizing tumor infiltrating lymphocytes.
−Removed: Some are pursuing CAR-T cells for solid tumors.
−Removed: In contrast, we are focused on developing TCR-T cell products against neoantigens arising from somatic mutations in solid tumors.
−Removed: Companies in the T-cell therapy segment that have target discovery platforms like ours include Adaptive Biotechnologies, Affini-T Therapeutics, Enara Bio, Immatics, Neogene Therapeutics (a member of the AstraZeneca group), PACT Pharma, T-knife Therapeutics, TScan Therapeutics and 3T Biosciences.
−Removed: Several companies, including Advaxis, Amgen, BioNTech, Geneos Therapeutics, and Gritstone, are pursuing vaccine platforms to target neoantigens for solid tumors.
−Removed: Other companies are developing non-viral gene therapies, including Poseida Therapeutics and several companies developing CRISPR technology, including Captain T Cell and Crispr Therapeutics.
−Removed: Several companies are pursuing the development of allogeneic CAR-T therapies, including Allogene Therapeutics, Atara Biotherapeutics and Precision Biosciences, which may compete with our product candidates.
−Removed: We also face competition from companies developing therapies using cells other than T cells, such as Athenex, Fate Therapeutics, ImmunityBio, IN8bio, Nkarta Therapeutics and Takeda Pharmaceutical.
−Removed: Other competitors are developing T cells with cytokines, such as Fate Therapeutics and Obsidian Therapeutics.
−Removed: Finally, we also face competition from non-cellular treatments offered by other companies, such as Amgen, AstraZeneca, Bristol-Myers Squibb, Immatics, Immunocore, Incyte, Merck, Mirati and Roche.
−Removed: We face competition on a broader spectrum of the oncology market that is more common, cost-effective and reimbursable, such as surgery, radiation and other drug therapies like chemotherapy, hormone therapy, biologic therapy such as monoclonal and bispecific antibodies, or a combination of any of these therapies.
−Removed: If any of our TCR-T therapies are approved, they may not be as competitive as other therapies, to the extent they are used in combinations with these therapies.
−Removed: Insurers and other third-party payors may also encourage use of certain products;
−Removed: thus, gaining market acceptance or market share for any of our TCR-T therapies could pose difficulties.
−Removed: Finally, standard of care could evolve or change throughout the clinical development of our product candidates.
+Added: These competitors include 2Seventy Bio, Achilles Therapeutics, Adaptimmune Therapeutics, Affini-T Therapeutics, Annoca, ArsenalBio, BioNTech, Bristol-Myers Squibb, Immatics, Iovance Biotherapeutics, Kite (a Gilead company), Lion TCR, Lyell Immunopharma, Medigene, Nurix Therapeutics, Neogene Therapeutics (a member of the AstraZeneca group), NexImmune, PACT Pharma, Precigen, Tactiva Therapeutics, Takara Bio, TCR 2 Therapeutics, T-Cure BioScience, T-knife Therapeutics, Triumvira Immunologics, TScan Therapeutics, Turnstone Biologics, Zelluna Immunotherapy and others.
Moreover, if our competitors develop and market a drug that is safer, more effective with fewer side effects, easier to administer, or less expensive, we could see a less favorable market opportunity for our TCR-T therapy candidates.
3 unchanged sentences
As of March 1, 2025, we had 1 full-time employee who is engaged in administration and no part-time employees.
−Removed: None of our employees are subject to a collective bargaining agreement and we believe our relations with our employees are good.
+Added: Our employee is not subject to a collective bargaining agreement.
+Added: In addition, we have engaged various consultants with our material consulting agreement being described below.
Our human capital resources objectives include identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees.
We endeavor to recruit the best people for the position regardless of gender, ethnicity or other protected traits and it is our policy to fully comply with all laws applicable to discrimination in the workplace.
−Removed: Our diversity, equity and inclusion principles are also reflected in our employee training and policies.
The principal purposes of our equity incentive plans are to attract, retain and motivate selected employees, consultants and directors through the granting of stock-based compensation awards and cash-based performance bonus awards.
−Removed: In 2023 and the first quarter of 2024, we entered into several material consulting agreements to ensure smooth transitions and business continuity.
−Removed: The Boyle Separation Agreement and Consulting Agreement
−Removed: On December 22, 2023, we entered into a Separation and Release Agreement, effective December 22, 2023, with Kevin S.
−Removed: (the “Separation Agreement”), the Company’s Chief Executive Officer, in connection with Mr.
−Removed: Boyle’s termination.
−Removed: Pursuant to the terms of his employment agreement, upon his termination Mr.
−Removed: Boyle was deemed to automatically resign from our Board of Directors.
−Removed: Pursuant to the terms of the Separation Agreement, and subject to customary conditions, we agreed to pay Mr.
−Removed: Boyle a one-time separation payment in an amount equal to six months of Mr.
−Removed: Boyle’s base salary and the cost of six months of COBRA premiums for Mr.
−Removed: Boyle, or approximately $331,990 less all applicable income and payroll taxes, deductions and withholdings.
−Removed: Boyle has agreed to make himself reasonably available to us to provide information related to his transition.
−Removed: The Separation Agreement also provides for a customary mutual release of all claims by us and Mr.
−Removed: Boyle against one another.
−Removed: We also entered into a consulting agreement (the “Boyle Consulting Agreement”), effective January 1, 2024, with Mr.
−Removed: Boyle pursuant to which he will continue providing strategic and advisory services to us.
−Removed: The Boyle Consulting Agreement will continue for a period of six months.
−Removed: The Boyle Consulting Agreement provides for compensation at a fixed rate of $15,000 per month and reimbursement for any usual and customary expenses incurred by Mr.
+Added: We continue to have in place several material consulting agreements to ensure business continuity.
+Added: The Boyle Consulting Agreement
+Added: On January 1, 2024, we also entered into a consulting agreement (the “Boyle Consulting Agreement”) with Mr.
+Added: our former Chief Executive Officer and Director, pursuant to which he provided strategic and advisory services to us.
+Added: The Boyle Consulting Agreement had a six months term.
+Added: The Boyle Consulting Agreement provided for compensation at a fixed rate of $15,000 per month and reimbursement for any usual and customary expenses incurred by Mr.
Boyle in connection with performing services pursuant to the Boyle Consulting Agreement.
−Removed: The Deniger Separation and Lackey Separation & Consulting Agreements
−Removed: As previously reported, on November 10, 2023, we terminated the employment of Melinda Lackey, Senior Vice President, Legal and Administration, and Drew Deniger, Vice President, Research and Development, “Without Cause” (as defined in their respective employment agreements) and, per their respective retention agreements, not because either failed to perform their duties at an “Acceptable Level” (as defined therein), effective November 15, 2023.
−Removed: In connection with their termination, we paid $44,998 to Ms.
−Removed: Lackey pursuant to her retention letter agreement, dated August 14, 2023, and $45,623 to Dr.
−Removed: Deniger pursuant to his retention letter agreement, dated September 1, 2023.
−Removed: The Deniger Separation Agreement
−Removed: Pursuant to the terms of the separation and release agreement between us and Dr.
−Removed: Deniger (the “Deniger Separation Agreement”), Dr.
−Removed: Deniger has agreed to remain reasonably available to the Company, and to reasonably cooperate and assist us, in connection with (i) any investigations, litigation or other proceedings in which he was involved while an employee and (ii) our consideration of strategic alternatives relating to its scientific assets.
−Removed: Subject to customary conditions, we paid Dr.
−Removed: Deniger a one-time separation payment in an amount equal to $182,500, less all applicable income and payroll taxes, deductions and withholdings.
−Removed: The Deniger Separation Agreement also provides for a customary release of all claims against us by Dr.
−Removed: The Lackey Separation Agreement and Consulting Agreement
−Removed: Pursuant to the terms of the separation and release agreement between us and Ms.
−Removed: Lackey (the “Lackey Separation Agreement”), Ms.
−Removed: Lackey agreed to remain reasonably available to the Company, and to reasonably cooperate and assist us, in connection with any investigations, litigation or other proceedings in which she was involved while an employee.
−Removed: Subject to customary conditions, we paid Ms.
−Removed: Lackey a one-time separation payment in an amount equal to $180,000, less all applicable income and payroll taxes, deductions and withholdings.
−Removed: The Lackey Separation Agreement also provides for a customary release of all claims against us by Ms.
−Removed: We also entered into a consulting agreement (the “Lackey Consulting Agreement”), effective November 16, 2023, with Ms.
−Removed: Lackey pursuant to which Ms.
−Removed: Lackey will continue providing legal services to us, including assisting in its ongoing exploration of strategic alternatives.
+Added: The Lackey Consulting Agreement
+Added: Lackey, our former Senior Vice President, Legal & Administration, continues to be engaged by us under her consulting agreement , effective November 16, 2023, (the “Lackey Consulting Agreement”) pursuant to which Ms.
+Added: Lackey continues to provide legal and administrative services to us.
The Lackey Consulting Agreement will continue indefinitely until terminated by the Company or Ms.
2 unchanged sentences
Lackey in connection with performing services pursuant to the Lackey Consulting Agreement.
−Removed: Wong's Departure and Mr.
−Removed: Groenewald Engagement
−Removed: On February 15, 2024, Michael Wong gave notice of his resignation as Vice President, Finance, of the Company effective February 23, 2024.
−Removed: On February 22, 2024, the Company and Ferdinand Groenewald entered into a consulting agreement (the “Consulting Agreement”), effective February 22, 2024, pursuant to which Mr.
+Added: Groenewald's Engagement
+Added: On February 22, 2024, the Company and Ferdinand Groenewald entered into a consulting agreement (the “Groenewald Consulting Agreement”), effective February 22, 2024, pursuant to which Mr.
Groenewald will lead accounting and financial reporting activities of the Company.
−Removed: Groenewald will serve as the Company’s Vice President, Finance.
−Removed: The Consulting Agreement will continue indefinitely until terminated by either party upon 30 days’ advance notice.
−Removed: The Consulting Agreement provides for compensation at a fixed rate of $15,000 per month and reimbursement by the Company for any usual and customary business expenses incurred by Mr.
−Removed: Groenewald in connection with performing services pursuant to the Consulting Agreement.
−Removed: In addition, the Consulting Agreement provides for the Company to indemnify Mr.
+Added: Groenewald will serve as the Company’s Vice President, Finance taking over from Mr.
+Added: Wong our former Vice President of Finance.
+Added: The Groenewald Consulting Agreement will continue indefinitely until terminated by either party upon 30 days’ advance notice.
+Added: The Groenewald Consulting Agreement provides for compensation at a fixed rate of $15,000 per month and reimbursement by the Company for any usual and customary business expenses incurred by Mr.
+Added: Groenewald in connection with performing services pursuant to the Groenewald Consulting Agreement.
+Added: In addition, the Groenewald Consulting Agreement provides for the Company to indemnify Mr.
Groenewald on terms customary for officers.
−Removed: Since July 2022, Mr.
−Removed: Groenewald, age 39, has served in several capacities at the CFO Squad, which provides outsourced accounting and consulting services.
−Removed: From January 2, 2022 to July 31, 2022, Mr.
−Removed: Groenewald had served as the Chief Accounting Officer of Muscle Maker, Inc., a Nasdaq-listed company.
−Removed: From September 2018 to January 2, 2022, Mr.
−Removed: Groenewald served as the Chief Financial Officer of Muscle Maker,
−Removed: From January 25, 2018 through May 29, 2018, Mr.
−Removed: Groenewald served as the Vice President of Finance, Principal Financial Officer and Principal Accounting Officer of Muscle Maker, Inc., Muscle Maker Development, LLC and Muscle Maker Corp., LLC.
−Removed: In addition, from October 2017 through May 29, 2018, he served as the controller of Muscle Maker, Inc.
−Removed: Groenewald is a certified public accountant with significant experience in finance and accounting.
−Removed: From July 2018 through August 2018, he served as senior financial reporting accountant of Wrinkle Gardner & Company, a full-service tax, accounting and business consulting firm.
−Removed: From February 2017 to October 2017, Mr.
−Removed: Groenewald served as Senior Financial Accounting Consultant at Pharos Advisors, Inc.
−Removed: serving a broad range of industries.
−Removed: From November 2013 to February 2017, he served as a Senior Staff Accountant at Financial Consulting Strategies, LLC, where he provided a broad range of accounting, financial reporting, and pre-auditing services to various industries.
−Removed: From August 2015 to December 2015, Mr.
−Removed: Groenewald served as a Financial Reporting Analyst at Valley National Bank.
−Removed: Groenewald holds a Bachelor of Science in accounting from the University of South Africa.
−Removed: Groenewald has served as a member of the Board of Directors of (i) HeartCore Enterprises, Inc., a company listed on the Nasdaq Capital Market, since January 24, 2022;
−Removed: (ii) SYLA Technologies Co., Ltd., a publicly reporting company that is listed on the Nasdaq Capital Market, since December 1, 2022;
−Removed: and (iii) Sushi Ginza Onodera, Inc., a company that has publicly filed a registration statement on Form S-1 in connection with its initial public offering, since July 1, 2023.
Corporate Information
17 unchanged sentences
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.