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Item 1. Business

2023-03-30 compared with 2022-02-28 · 712 added, 688 removed, 1518 unchanged (48% of the section changed)

We are a clinical stage drug discovery, development and manufacturing company focused on deploying our proprietary integrated cell-free protein synthesis platform, XpressCF ®, and our site-specific conjugation platform, XpressCF+ ®TM , to create a broad variety of optimally designed, next-generation protein therapeutics, initially for cancer.

We aim to design therapeutics using the most relevant and potent modalities, including cytokine-based therapeutics, immuno-oncology, or I/O agents, antibody-drug conjugates, or ADCs, immunostimulatory ADCs, or iADCs, and bispecific antibodies that are directed primarily against clinically validated targets where the current standard of care is suboptimal.

We believe our platform allows us to accelerate the discovery and development of potential first-in-class and best-in-class molecules by enabling the rapid and systematic evaluation of protein structure-activity relationships to create optimized homogeneous product candidates.

Our mission is to transform the lives of patients by using our XpressCF ® platform to create medicines with improved therapeutic profiles for areas of unmet need.

Our two most advanced product candidates are wholly owned:

STRO-002, an ADC directed against folate receptor-alpha, or FolRα, for patients with FolRα-expressing cancers, such as ovarian and endometrial cancers, and STRO-001, an ADC directed against CD74, for patients with B-cell malignancies, such as multiple myeloma and non-Hodgkin lymphoma, or NHL.

In March 2019, STRO-002 began enrolling patients in a Phase 1 trial focused on ovarian and endometrial cancers.

The dose escalation portion of the STRO-002 Phase 1 trial has been completed and the dose expansion portion of the trial is ongoing to assess the efficacy, safety and tolerability of STRO-002 at dose levels of 4.3 and 5.2 mg/kg .

In May 2021, we reported data from the dose-escalation cohort.

Based on such reported data, STRO-002 exhibited a manageable safety profile and promising preliminary efficacy data, as discussed in more detail below.

In January 2022, we released initial results of the dose expansion portion of the STRO-002 Phase 1 trial.

These data suggested that STRO-002 exhibited a manageable safety profile together with promising preliminary efficacy data in the tested patient population, as discussed in more detail below.

In August 2021, we were granted Fast Track designation for STRO-002 by the U.S.

We are a clinical-stage oncology company developing site-specific and novel-format antibody drug conjugates, or ADCs, enabled by our proprietary integrated cell-free protein synthesis platform, XpressCF ® , and our site-specific conjugation platform, XpressCF+ ® .

We aim to design and develop therapeutics using the most relevant and potent modalities, including ADCs, bispecific ADCs, immunostimulatory ADCs, or iADCs, dual conjugate ADCs, or ADC 2 s, and cytokine derivatives.

Our molecules are directed primarily against clinically validated targets where the current standard of care is suboptimal.

We believe that our platform allows us to accelerate the discovery and development of potential first-in-class and/or best-in-class molecules by enabling the rapid and systematic evaluation of protein structure-activity relationships to create optimized homogeneous product candidates.

Our mission is to transform the lives of patients by creating medicines with improved therapeutic profiles for areas of unmet need.

Our most advanced product candidate is STRO-002, or luveltamab tazevibulin, or luvelta, an ADC directed against folate receptor-alpha, or FolRα, for patients with FolRα-expressing cancers, including ovarian cancer.

In 2019, we began enrolling patients in a Phase 1 trial of luvelta that focused on ovarian and endometrial cancers.

The dose escalation portion of the luvelta Phase 1 trial has been completed and the dose expansion portion of the trial to assess the efficacy, safety and tolerability of luvelta is ongoing.

In January 2023 we reported preliminary final results from the dose-expansion cohort.

The data from the dose-escalation and dose expansion cohorts suggested that luvelta exhibited a manageable safety profile together with promising preliminary efficacy data in the tested patient population, as discussed in detail below.

In August 2021, luvelta was granted Fast Track designation by the U.S.

Food and Drug Administration, or FDA, for the treatment of patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior lines of systemic therapy.

In December 2021, we entered into a licensing agreement with Tasly Biopharmaceuticals Co., Ltd, or Tasly, to grant Tasly an exclusive license to develop and commercialize STRO-002 in China, Hong Kong, Macau and Taiwan, referred to as Greater China (the “Tasly License Agreement”).

Our second candidate, STRO-001, is currently enrolling patients in a Phase 1 trial, with updated data reported in December 2020, as discussed in more detail below.

Based on such reported data, STRO-001 has been generally well-tolerated and, unlike certain other ADCs, no ocular toxicity signals have been observed, with no patients receiving prophylactic corticosteroid eye drops.

Dose escalation in the STRO-001 Phase 1 trial is continuing, and the maximum tolerated dose has not yet been reached.

In October 2018, we were granted Orphan Drug Designation by the FDA for STRO-001 for the treatment of multiple myeloma.

In October 2021, we granted BioNova Pharmaceuticals Limited, or BioNova, an option to exclusively license the right to develop and commercialize STRO-001 in Greater China (the “BioNova Option Agreement”).

Based on our proprietary XpressCF ® and XpressCF+ ®TM platforms, we have also entered into multi-target, product-focused collaborations with leaders in the field of oncology, including a cytokine derivatives collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, or Merck;

a B Cell Maturation Antigen, or BCMA, ADC collaboration with Celgene Corporation, or Celgene, a wholly owned subsidiary of Bristol-Myers Squibb Company, New York, NY, or BMS;

a MUC1-EGFR ADC collaboration with Merck KGaA, Darmstadt Germany (operating in the United States and Canada under the name “EMD Serono”);

and license agreement to develop and commercialize STRO-002 in Greater China with Tasly.

Our XpressCF ® and XpressCF+ ®TM platforms have also supported a spin-out company, Vaxcyte Inc., or Vaxcyte, focused on discovery and development of vaccines for the treatment and prophylaxis of infectious disease.

In mid-2022, we discussed with the FDA appropriate trial designs for a registration-directed trial of luvelta to potentially support accelerated approval.

We expect to begin a registration-directed trial of luvelta for platinum-resistant ovarian cancer in the first half of 2023.

In addition, we have been offering compassionate use of luvelta to treat pediatric patients with relapsed/refractory CBFA2T3-GLIS2, or CBF/GLIS, acute myeloid leukemia, or AML, commonly known as RAM phenotype AML.

Compassionate use data showed anti-leukemic activity of luvelta in pediatric patients with relapsed/refractory CBF/GLIS AML and was presented at the 64th American Society of Hematology Annual Meeting and Exposition (ASH 2022) in December 2022.

The data showed that luvelta was well tolerated as a monotherapy agent and in combination with standard cancer therapies.

Luvelta was granted Orphan Drug Designation by the FDA in December 2022 in this pediatric patient population.

Our next most advanced product candidate is STRO-001, an ADC directed against CD74, for patients with B-cell malignancies, such as multiple myeloma and non-Hodgkin lymphoma, or NHL.

We have an ongoing Phase 1 trial of STRO-001 for the treatment of multiple myeloma and NHL.

STRO-001 has been granted Orphan Drug Designation by the FDA for the treatment of multiple myeloma.

Our most recent data update was provided in December 2020, as discussed in more detail below.

Based on such reported data, STRO-001 has been generally well-tolerated.

We have completed dose escalation in the STRO-001 Phase 1 trial following identification of the maximum tolerated dose.

In October 2021, we granted BioNova Pharmaceuticals Limited, or BioNova, an option to exclusively license the right to develop and commercialize STRO-001 in Greater China, or the BioNova Option Agreement.

In February 2023, BioNova announced that the first patient had been dosed in the Phase 1 clinical trial of STRO-001.

We also have a preclinical product candidate - STRO-003, which is a single homogeneous ADC directed against an anti-receptor tyrosine kinase-like orphan receptor 1, or ROR1, which we intend to develop for the treatment of solid tumors.

Preparations are underway for IND-enabling studies for STRO-003, which we expect will be completed in the first quarter of 2024.

Enabled through our proprietary XpressCF ® and XpressCF+ ® platforms, we have entered into multi-target, product-focused collaborations with leading pharmaceutical and biotechnology companies in the field of oncology, including an immunostimulatory antibody-drug conjugates collaboration with Astellas Pharma Inc., or Astellas, a cytokine derivatives collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, or Merck;

a B Cell Maturation Antigen, or BCMA, ADC collaboration with Celgene Corporation, or Celgene, a

wholly owned subsidiary of Bristol Myers Squibb Company, New York, NY, or BMS;

a MUC1-EGFR ADC collaboration with Merck KGaA, Darmstadt Germany (operating in the United States and Canada under the name “EMD Serono”), or EMD Serono.

Our XpressCF ® and XpressCF+ ® platforms have also supported Vaxcyte, Inc., or Vaxcyte, focused on discovery and development of vaccines for the treatment and prophylaxis of infectious disease.

In the fourth quarter of 2022, Vaxcyte announced positive topline data from a Phase 1/2 clinical proof-of-concept study of its lead product candidate, VAX-24, its 24-valent pneumococcal conjugate vaccine candidate, under investigation for the prevention of invasive pneumococcal disease in adults aged 18-64.

Also in the fourth quarter of 2022, we entered into an agreement with Vaxcyte, granting it an option to access expanded rights to develop and manufacture cell-free extract for use in development and manufacture of its vaccine products, among certain other rights.

We believe our XpressCF ® platform is the first and only current Good Manufacturing Practices, or cGMP, compliant and scalable cell-free protein synthesis technology that has resulted in multiple product candidates in clinical development.

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We plan to leverage these capabilities to accelerate the discovery and development of potential first-in-class and best-in-class molecules.

The benefits of our XpressCF ® and XpressCF+ ®TM platforms have resulted in collaborations with leaders in the field of oncology, including Merck, BMS and EMD Serono.

As a result of discovery efforts enabled through our XpressCF ® and XpressCF+ ®TM platforms, Merck has the right to develop two cytokine derivative candidate molecules.

Additionally, BMS has the worldwide right to develop and commercialize a novel ADC therapeutic directed against BCMA, known as CC-99712.

An IND submission was filed in connection with CC-99712 in the first half of 2019.

CC-99712 is being studied in a Phase 1 trial, as a monotherapy and in combination with a gamma secretase inhibitor, and is currently enrolling patients with relapsed and refractory multiple myeloma.

In February 2021, CC-99712 was granted orphan drug designation for the treatment of relapsed and refractory multiple myeloma.

Finally, our collaboration with EMD Serono yielded a novel bispecific ADC product candidate targeting EGFR and MUC1, known as M1231, for which an IND submission was filed in the second half of 2020 and which is currently under investigation in a Phase 1 trial for the treatment of solid tumors, including metastatic non-small cell lung cancer and esophageal squamous cell carcinoma.

The benefits of our XpressCF ® and XpressCF+ ® platforms have resulted in collaborations with leaders in the field of oncology, including Astellas, Merck, BMS and EMD Serono.

In 2022, we entered into a License and Collaboration Agreement with Astellas, for the development of immunostimulatory antibody-drug conjugates for up to three biological targets.

Our collaboration with Merck resulted in MK-1484, a selective IL-2 agonist that Merck is developing as a monotherapy and in combination with pembrolizumab for the treatment of solid tumors.

We announced the dosing of the first patient with MK-1484 in a Phase I study in the third quarter of 2022.

Our BMS collaboration yielded CC-99712, a novel ADC therapeutic directed against BCMA.

BMS is studying CC-99712 in a Phase 1 trial initiated in 2019, both as a monotherapy and in combination with a gamma secretase inhibitor, in patients with relapsed and refractory multiple myeloma.

CC-99712 has been granted orphan drug designation for the treatment of relapsed and refractory multiple myeloma.

Finally, our collaboration with EMD Serono yielded a novel bispecific ADC product candidate targeting EGFR and MUC1, known as M1231, for which an IND submission was filed in 2020.

Recently, EMD Serono decided to close the Phase 1a trial of M1231 in patients with solid tumors and not initiate a previously planned expansion study.

EMD Serono stated that the decision was based on strategic portfolio considerations.

Through December 31, 2022, we have received an aggregate of approximately $621 million in payments from all of our collaborations, which includes approximately $54 million in investments in our stock.

We intend to selectively enter into additional collaborations with partners who are seeking efficient and effective drug discovery, preclinical development and manufacturing capabilities for the creation of novel therapeutics.

Our first internally developed product candidate is STRO-001, which we believe has the potential to be a first-in-class and best-in-class ADC directed against CD74, an antigen that is highly expressed in many B cell malignancies.

In multiple preclinical models, STRO-001 has demonstrated potent anti-tumor activity.

In addition, the properties of STRO-001 suggest a low likelihood of off-target toxicity and potential for an improved therapeutic index.

STRO-001 is currently enrolling patients in a Phase 1 trial for multiple myeloma and NHL for which we reported updated data in December 2020.

Based on such reported data, STRO-001 has been generally well-tolerated and no ocular toxicity signals have been observed, with no patients receiving prophylactic corticosteroid eye drops.

Dose escalation in the STRO-001 Phase 1 trial is continuing, and the maximum tolerated dose has not yet been reached.

We expect to identify a recommended Phase 2 dose for STRO-001 by the end of 2022.

As discussed above, we are developing luvelta for the treatment of ovarian and endometrial cancers.

In addition to the development discussed above, an expansion cohort assessing the effects of administration of prophylactic pegfilgrastim in combination with luvelta opened for enrollment in the second quarter of 2022;

interim results from this cohort were presented in January 2023.

Other studies ongoing for luvelta include a trial assessing the combination of luvelta with bevacizumab for treatment of ovarian cancer and an expansion cohort for FolRα-selected endometrial cancer that opened for enrollment in the fourth quarter of 2021.

Additionally, luvelta was provided to pediatric patients with CBF/GLIS AML on a compassionate use basis.

Translational work is also ongoing to support an investigational new drug, or IND, application for the initiation of a non-small cell lung cancer study, for which submission is planned in 2023.

In December 2021, we entered into the Tasly License Agreement, as amended in April 2022, to develop and commercialize luvelta in the Greater China territory.

We believe that our collaboration with Tasly extends the opportunity to realize the potential value of luvelta through clinical development and commercialization in Greater China.

We have also been internally developing STRO-001, which we believe has the potential to be a first-in-class and best-in-class ADC directed against CD74, an antigen that is highly expressed in many B cell malignancies.

We have completed enrollment for STRO-001 dose escalation in a Phase 1 trial for multiple myeloma and NHL.

STRO-001 has been generally well-tolerated and no ocular toxicity signals have been observed, with no patients receiving prophylactic corticosteroid eye drops.

The maximum tolerated dose of STRO-001 has been identified.

In October 2021, we entered into the BioNova Option Agreement.

We believe that our collaboration with BioNova extends the opportunity to realize the potential value of STRO-001 through clinical development and commercialization in Greater China.

We are also internally developing STRO-002, an ADC directed against FolRα, initially targeted for the treatment of ovarian and endometrial cancers.

Our experiments show that FolRα

expression can be detected in 90% or more of ovarian and endometrial cancers.

In preclinical models, STRO-002 has demonstrated the potential for enhanced and selective activity against cells expressing FolRα, superior inhibition of tumor growth and greater linker stability, in comparison to experiments we conducted with a benchmark FolRα-targeting molecule.

We began enrolling patients in a STRO-002 Phase 1 trial focused on ovarian and endometrial cancers in March 2019.

We have completed the dose-escalation portion of the trial and reported updated data for STRO-002 in May 2021.

The dose-expansion portion of the trial has been fully enrolled and is ongoing to assess the efficacy, safety and tolerability of STRO-002 at dose levels of 4.3 and 5.2 mg/kg.

For the dose-expansion portion, we dosed the first patient in January 2021 and are enrolling less heavily pre-treated ovarian cancer patients.

We reported initial dose-expansion data in January 2022.

Additionally, a STRO-002 combination cohort in ovarian cancer opened for enrollment in December 2021, assessing the combination of STRO-002 with bevacizumab, and an expansion cohort for FolR α

-selected endometrial cancer opened and began enrolling patients in the fourth quarter of 2021.

In December 2021, we entered into the Tasly License Agreement.

We believe that our collaboration with Tasly extends the opportunity to realize the potential value of STRO-002 through clinical development and commercialization in Greater China.

Although we believe our product candidates have the potential to be first-in-class and/or best-in-class and to provide potent anti-tumor activity with reduced off-target toxicity, we will need to complete additional studies to determine the safety and efficacy of our product candidates.

The results of these future studies may be different than the results of our earlier studies.

We have not received regulatory approval for any of our product candidates, and in order to obtain regulatory approval and commercialize our product candidates, the FDA or foreign regulatory agencies will need to determine that our product candidates are safe and effective.

We may not obtain regulatory approval on the timeline we currently expect, or at all, and competing therapies and products may ultimately reach the market faster or have more favorable safety and efficacy profiles than our product candidates.

Beyond these wholly owned programs and collaborations, we are developing a broader pipeline of next-generation protein therapeutics using our XpressCF ® and XpressCF+ ®TM platforms.

In February 2023, BioNova announced that the first patient had been dosed in the Phase 1 clinical trial of STRO-001 in which BioNova will conduct further dose optimization.

We are also developing STRO-003, which we believe has the potential to be a first-in-class and best-in-class ADC targeting ROR1.

Preclinical data suggest that STRO-003 has potent antitumor activity and potential for a differentiated safety profile.

Preparations are underway for IND-enabling studies for STRO-003, which we expect will be completed in the first quarter of 2024.

Beyond these programs and collaborations, we are developing a broader pipeline of next-generation protein therapeutics using our XpressCF ® and XpressCF+ ® platforms.

Our protein engineering and chemistry efforts are focused on maximizing therapeutic indices, and our technology allows us to rapidly test our therapeutic hypothesis in significantly more product candidates than conventional protein synthesis allows in order to identify the best molecule to advance to the clinic.

Our drug discovery teams are exploring novel immuno-oncology therapies, including cytokine-based therapies.

We are also actively pursuing the discovery and development of other novel ADCs, including tumor targeting immunostimulant-ADCs, or iADCs and bispecific antibodies, including T cell-engager discovery programs.

We are also actively pursuing the discovery and development of other novel ADCs, including iADCs, bispecific ADCs, and ADC 2 s.

Our goal is to use our proprietary XpressCF ® platform to create product candidates primarily against clinically validated targets.

Key elements of our strategy are to:

Advance STRO-001 and STRO-002 through clinical development.

We are currently evaluating STRO-001 in a Phase 1 trial for patients with advanced and/or refractory multiple myeloma and NHL.

Based on our preclinical data, we believe STRO-001 has the potential to be a first-in-class and best-in-class ADC directed against CD74, which is highly expressed in many B cell malignancies.

We reported updated data in December 2020, expect to establish a recommended Phase 2 dose in 2022, and thereafter may begin the dose expansion portion of the Phase 1 trial.

In October 2018, we were granted Orphan Drug Designation by the FDA for STRO-001 for the treatment of multiple myeloma.

In October 2021, we entered into the BioNova Option Agreement for STRO-001 in Greater China.

We began enrolling patients in a STRO-002 Phase 1 trial focused on ovarian and endometrial cancers in March 2019 and dosed the first patient in the dose expansion portion of the Phase 1 trial in January 2021, enrolling less heavily pre-treated ovarian cancer patients.

We reported updated dose-escalation data in December 2020 and May 2021 and reported initial dose-expansion data in January 2022.

In December 2021, we entered into the Tasly License Agreement for STRO-002 in Greater China.

Advance luvelta through clinical development.

We began enrolling patients in a luvelta Phase 1 trial focused on advanced ovarian and endometrial cancers in March 2019 and dosed the first patient in the dose expansion portion of the Phase 1 trial in January 2021.

We reported updated dose-escalation data in December 2020 and May 2021 and reported dose-expansion data in January 2022 and January 2023.

In December 2022, we announced that data was presented resulting from compassionate use of luvelta in pediatric patients with relapsed/refractory CBF/GLIS AML.

Given that FolRα

is a clinically validated target for ovarian cancer, along with STRO-002’s homogeneous design, we believe it

has the potential to be a best-in-class FolRα-targeted ADC and provide greater activity, stability and safety as compared to other investigational agents in development.

Maintain worldwide rights to our core product candidates to the extent possible and collaborate with partners to develop and commercialize our core product candidates in certain territories.

We own the worldwide commercial rights to our most advanced product candidates, STRO-001 and STRO-002, except for the rights granted to BioNova and Tasly, respectively, in certain territories.

is a clinically validated target for ovarian cancer, along with luvelta’s homogeneous design, we believe it has the potential to be a best-in-class FolRα-targeted ADC and provide benefit to a broader patient population, as well as potentially greater activity, stability and safety as compared to other investigational agents in development.

Maintain worldwide rights or, where appropriate, U.S.

rights to our core product candidates to the extent possible and collaborate with partners to develop or co-develop and commercialize or co-commercialize our core product candidates in certain territories.

We have assembled a management team with extensive experience in the biopharmaceutical industry, including drug discovery and development through commercialization, and our plan is to independently pursue the development and commercialization of our product candidates.

As we continue to advance our products, we may opportunistically pursue additional strategic partnerships that maximize the value of our pipeline.

As we continue to advance our products, we may opportunistically pursue additional strategic partnerships that maximize the value of our pipeline, including relationships to potentially co-develop and co-commercialize one or more of our product candidates.

Develop a diverse pipeline of novel product candidates with optimal therapeutic profiles.

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Our cell-free-based protein synthesis system enables the rapid and systematic evaluation of protein structure-activity relationships, which we believe will accelerate the discovery and development of molecules.

We aim to take advantage of the most potent modalities, including cytokines, ADCs, iADCs and bispecific antibodies, to create drugs that are directed primarily against clinically validated targets where the current standard of care is suboptimal.

We aim to take advantage of the most potent modalities,

focusing primarily on ADCs, iADCs, bispecific ADCs and ADC 2 s, to create drugs that are directed primarily against clinically validated targets where the current standard of care is suboptimal.

Strategically pursue additional collaborations to broaden the reach of our XpressCF ® platform.

To maximize the value of our XpressCF ® platform technology, we have entered into multi-target, product-focused collaborations with leaders in the field of oncology, including a cytokine derivatives collaboration with Merck, a BCMA ADC collaboration with Celgene (now BMS) and a MUC1-EGFR ADC collaboration with EMD Serono.

To maximize the value of our XpressCF ® platform technology, we have entered into multi-target, product-focused collaborations with leaders in the field of oncology, including an iADC collaboration with Astellas, a cytokine derivatives collaboration with Merck, a BCMA ADC collaboration with BMS and a MUC1-EGFR ADC collaboration with EMD Serono.

We intend to selectively enter into additional collaborations with partners who are seeking efficient and effective drug discovery and manufacturing capabilities for the development of novel therapeutics.

We intend to retain certain development and commercial rights to maximize the future potential value of product candidates discovered and developed using our XpressCF ® platform.

Selectively expand the scope of our XpressCF ® platform into other therapeutic areas.

Due to the versatility of our platform, we can explore additional therapeutic areas outside of oncology.

We intend to make further investment in the development of our XpressCF ® platform to expand our pipeline of product candidates.

We intend to retain to the extent possible certain development and commercial rights to maximize the future potential value of product candidates discovered and developed using our XpressCF ® platform.

Cancer Remains a Major Unmet Medical Need

Cancer is the second leading cause of mortality in the United States and is the leading cause of death for those under 65 years of age.

The American Cancer Society estimated that there would be roughly 1.9 million new cases of cancer diagnosed and approximately 609,000 people would die of cancer in the United States in 2021.

The American Cancer Society estimated that there would be greater than 1.9 million new cases of cancer diagnosed and approximately 610,000 people would die of cancer in the United States in 2023.

Traditional Cancer Therapeutics

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Also, safety and tolerability concerns often limit the use of higher, potentially more efficacious doses.

We believe our

XpressCF ® platform will provide enhanced therapeutic approaches for treating cancer to address these unmet needs.

A new generation of biologics is emerging, including cytokine-based therapeutics, immuno-oncology agents, ADCs, iADCs and bispecific antibodies.

Additional modalities such as ADCs have shown promise over the last decade with fourteen approvals and over a hundred ADC candidates investigated in the clinic.

ADCs use the foundation of monoclonal antibodies and small molecule drugs by targeting the delivery of chemotherapeutics to the tumor.

They have shown clinical benefit in hematological and solid tumors, and often have a better safety profile than systemically delivered chemotherapeutics.

We believe our XpressCF ® platform will provide enhanced therapeutic approaches for treating cancer to address these unmet needs and are exploring next generation biologics, including ADCs, iADCs, and ADC 2 s.

The expectation is that multiple therapeutic modalities will be used in novel combinations to treat patients and provide the most potent anti-cancer effect.

Immuno-Oncology

The immune system is capable of recognizing and eliminating tumor cells.

However, some cancer cells over express proteins, called immune checkpoints, which suppress the immune system, and enable the tumor cells to evade destruction.

Immuno-oncology has emerged as a promising new therapeutic approach that aims to enhance anti-tumor immune responses by using monoclonal antibodies to overcome these immune checkpoint blockades.

Six monoclonal antibody immune checkpoint inhibitors are approved in the United States for the treatment of cancer indications, such as melanoma, non-small cell lung cancer, or NSCLC, renal cancer and bladder cancer.

Checkpoint inhibitors are among the leading cancer drugs, with Keytruda and Opdivo alone generating more than $22 billion in worldwide sales in 2020.

Limitations to Current Immuno-Oncology Approaches

The effectiveness of any cancer immunotherapy is dependent on the status of an individual patient’s immune system.

While many single-agent immunotherapies have resulted in remarkable clinical results, only a minority of patients have realized durable benefits from these treatments.

An immunotherapy cannot succeed if a patient’s immune cells are too impaired to benefit from a particular checkpoint inhibitor or cytokine-based therapeutic.

As a result, combination therapies have been explored clinically and are designed to provide an additional boost to revive a patient’s ability to mount an immune response against their tumor.

However, combination therapies will likely have to provide a significant risk-benefit advantage to justify the cumulative costs of combining two separate immunotherapies.

New single agent approaches to achieving combinatorial stimulation of a patient’s immune system may therefore create the preferred option for many patients and physicians.

Antibody-Drug Conjugates

Antibody-Drug Conjugates (ADCs)

After more than two decades of industry efforts, several new modalities of highly potent monoclonal antibody-based therapies have emerged, including ADCs.

The key components of ADCs include an antibody, a stable linker, and a cytotoxic agent (warhead).

The antibody is used to target and deliver the cytotoxic agent to tumor cells.

The antibody is used to target and deliver cytotoxic agents to tumor cells.

ADCs can be mono, bispecific, or multi-specific.

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Kadcyla and Adcetris were the first of the new generation of ADCs to be approved for the treatment of specific subsets of breast cancer and lymphoma, respectively.

Since the approval of Kadcyla, ten more ADCs entered or re-entered the market, as Besponsa, Mylotarg, Lumoxiti, Polivy, and Zynlonta were approved for the treatment of specific subsets of leukemia and lymphoma;

Several more ADCs are currently on the market in the U.S.:

Besponsa, Mylotarg, Lumoxiti, Polivy, Zynlonta, and Zevalin were approved for the treatment of specific subsets of leukemia and lymphoma;

Padcev was approved for the treatment of bladder and urinary tract cancers;

Enhertu and Trodelvy were approved for the treatment of breast cancer;

Blenrep was approved for the treatment of multiple myeloma;

and Tivdak was approved for the treatment of cervical cancer.

All twelve of these approved therapies demonstrate that ADCs have an emerging role in the armamentarium of cancer therapeutics.

Tivdak was approved for the treatment of cervical cancer;

and ELAHERE was approved for the treatment of ovarian cancer.

All of these approved therapies demonstrate that ADCs have an emerging role in the armamentarium of cancer therapeutics.

Limitations to Current ADC Approaches

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Heterogeneity as a Result of Imprecise and Variable Conjugation.

The approved ADCs and many that are in development use imprecise technologies that opportunistically attach the cytotoxic payload to naturally occurring amino acids within the antibody and result in a heterogeneous mixture.

Many ADCs, both those approved and those in development, use imprecise technologies that opportunistically attach the cytotoxic payload to naturally occurring amino acids within the antibody and result in a heterogeneous mixture.

In these mixtures, the number and site location of the linker-warhead can vary significantly from antibody to antibody within the single ADC product.

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We believe that superior ADCs can be developed using technologies that allow linker-warhead positioning to be fine-tuned to empirically determined sites for maximal therapeutic benefit .

Instability Due to Linker Design .

One of the major challenges in ADC technology has been to develop linking chemistries that ensure that warheads are only released from the antibody within a tumor cell, and not released within the blood or healthy tissue as the ADC is delivered systemically and travels through the body.

Lack of Tumor Specificity Due to Linker Design .

One of the major challenges in ADC technology has been to develop linking chemistries that ensure that warheads are only released from the antibody within the tumor microenvironment, and not released within the blood or healthy tissue as the ADC is delivered systemically and travels through the body.

We believe that safer ADCs can be developed by utilizing non-natural amino acids that enable state-of-the-art chemistries to ensure that the warhead is not prematurely released.

Bispecific Antibodies

Bispecific antibodies are engineered proteins that can simultaneously bind to two different types of antigens.

Targeting two individual antigens simultaneously is expected to drive a larger clinical impact than conventional monoclonal antibodies.

As a class, there are currently approximately 45 bispecific antibodies in clinical development for oncology indications.

Bispecific antibodies can be engineered in a variety of different formats as shown below.

Bispecific antibodies come in a wide variety of structural formats that can be used in multiple therapeutic modalities, including dual blocking bispecific antibodies, T cell-engaging bispecific antibodies and dual antigen targeting bispecific antibodies.

Given the potential synergistic nature of these approaches, they have the potential to provide a similar, if not improved, therapeutic benefit as compared to a traditional combination approach.

In addition, they may also demonstrate an improved safety and tolerability profile.

These characteristics could allow for a wider therapeutic index as compared to the comparable combination therapy approach.

Additionally, combining two mechanisms in a single bispecific antibody could have advantages in manufacturing, clinical development and patient convenience.

Limitations to Current Bispecific Antibody Approaches

Bispecific antibodies are highly engineered proteins with structural features not found in nature.

The generation of these molecules therefore presents significant design and development challenges, especially when using conventional cell-based technologies.

These challenges include:

Optimization Challenges.

Bispecific antibodies simultaneously engage two different targets and therefore have precise requirements for the binding properties and spatial orientation of each domain in order to have pharmacologic activity.

Combinatorial pairing of antibody binding arms to identify an optimized bispecific antibody requires many distinct cell lines that must be engineered during the discovery process, a cumbersome process when using conventional cell-based technologies.

Challenges to T Cell-Engagers.

Discovery of bispecific T cell-engagers is further limited by the challenge of designing bispecific pairs that can safely activate T cells specifically in the tumor environment without activating peripheral T cells, which would result in severe toxicities.

Difficulties in Protein Expression and Manufacturing.

Because bispecific antibodies are highly engineered proteins, conventional cell-based systems have significant difficulties in protein expression, particularly at a larger scale.

We believe that new protein engineering technologies will enable significantly broader design opportunities to discover new bispecific antibodies optimized for therapeutic activity, safety and manufacturability.

In addition, linker chemistries that rely on proteinases preferentially expressed in the tumor such as cathepsin and B-Glucuronidase, can provide more tumor specific release of the active catabolites and a resulting better safety profile.

Mechanism of Action of Cytotoxin Payloads.

Beyond potent cytotoxic activity of ADC payloads, there are additional attributes that lead to better efficacy and more durable responses.

Payloads that induce bystander activity which is dependent on the ADC target engagement, but also kills surrounding cells within the tumor, are thought to result in broader activity.

Additionally, some payloads can induce immunogenic cell death pathways.

These pathways not only cause potent tumor cell killing but also produce an immunological phenotype in the cancer cells that allow a secondary immune response and killing of the tumor.

Dual conjugations to enable iADC and ADC 2 modalities

XpressCF ® enables the incorporation of non-natural amino acids into antibody sequences and results in site specific conjugation of drug payloads.

More recently, we have developed technology to enable incorporation of two different non-natural amino acids that allows for the site-specific conjugation of two different payloads, providing the opportunity to combine pharmacology into a single molecule.

We believe this is the first use of dual conjugation combining a conventional cytotoxin with an immune stimulatory payload to drive not only direct killing of the tumor cells but an immune response against the tumor.

These iADC molecules utilize immune agonists such as TLR 7, TLR 8 and STING to induce activation of innate immune cells within the tumor microenvironment and resulted in more complete responses and protective anti-tumor immune responses in preclinical tumor models.

This dual conjugation approach is the basis for our research collaboration with Astellas that is focused on the discovery of iADC molecules for solid tumors.

In addition to immune modulators, additional payloads can be incorporated into our dual conjugation approach.

These ADC 2 payloads are focused on targets that are upregulated tumors that do not respond well to existing therapies.

Our goal is to provide more durable responses in hard-to-treat tumors by combining two payloads that may offset resistance mechanisms.

Cytokine-Based Immuno-Oncology Therapeutics

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The observed efficacy of a modified cytokine, in combination with an immune checkpoint inhibitor, indicates the potential of this new approach.

In light of these data and our prior research into cytokines, we commenced a cytokine-based research program using our XpressCF ® and XpressCF+ ®TM platform technologies and are now collaborating with Merck on developing cytokine derivatives.

In light of these data and our prior research into cytokines, we commenced a cytokine-based research program using our XpressCF ® and XpressCF+ ® platform technologies to engineer cytokines aimed at better exposure and tolerability profiles.

Our collaboration with Merck focused on developing cytokine derivatives yielded an IL-2 derivative that entered Phase 1 in 2022.

We believe that recent advances in immuno-oncology combined with new protein engineering technologies create opportunities to identify novel cytokine-based therapeutics with superior therapeutic indexes.

Our Proprietary XpressCF ® Platform

While cytokine-based immuno-oncology therapeutics, ADCs, iADCs and bispecific antibodies hold significant promise, drug developers working with these complex biologics face significant design and development challenges.

While ADCs, iADCs, ADC 2 s and engineered cytokines hold significant promise, drug developers working with these complex biologics face significant design and development challenges.

Optimizing these complex biological structures is a challenging, trial and error process that requires the refinement of several properties in tandem.

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We believe our cell-free-based protein synthesis technology allows for efficient and proper design exploration to be conducted prior to nominating a lead drug candidate.

In addition, we believe we can optimally design these types of complex biologics in a manner that is ideal for subsequent production at relevant scale and manufacture.

In addition, we believe we can optimally design these types of complex biologics in a

manner that is ideal for subsequent production at relevant scale and manufacture.

We believe we are the only company with products in clinical development that has the capability to produce cell-free-based protein synthesis at scale.

We believe we have a significant advantage over other development approaches in this space.

Limitations of Current Cell-Based Synthesis Approaches

All existing therapeutic proteins rely on cell-based design, production and manufacturing technologies.

The conventional biotechnology approach for the production of these complex biologics relies primarily on CHO cell lines.

This first requires low yield transient production from cells that enable characterization of a new protein over several months.

This is then followed by development of stable cell lines over several months to a year to enable larger scale preclinical, clinical and commercial production.

The characterization process has to be reproduced for every minor variant of the therapeutic protein, which may or may not result in improved properties.

Each change requires development of new cell-based methods to generate protein of sufficient quality and quantity to evaluate.

Therefore, it is extremely laborious and resource intensive to elucidate principles of structure-activity relationship, and drug discovery is limited by the number of cell lines that can be practically managed in parallel.

In addition, they have limited ability to introduce non-natural amino acids into proteins.

We believe these limitations hinder the efficiency of drug discovery and often result in suboptimal protein selection.

Overview of Our XpressCF ® Platform

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Advantages of Our XpressCF ® Platform

We believe our drug discovery platform provides significant advantages over conventional cell-based protein synthesis approaches and has the ability to produce a large number of variants during the development stage, while preserving the ability to design and test large families of molecules for optimized efficacy and safety features.

As a result, we believe that our drug discovery platform can accelerate time to IND by nine to fifteen months compared to conventional technologies.

We believe the advantages of our cell-free-based protein synthesis technology platform include:

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By decoupling the production of the cell-free extract from the production of the protein, we are able to stockpile large quantities of cell-free extract from which we are able to manufacture a wide variety of proteins without the need to generate individual cell lines, including cytokine-based immuno-oncology therapeutics, ADCs, iADCs and bispecific antibodies.

Additionally, our dual conjugation ADC 2 technology could enable “mixed payload”

ADCs that combine two distinct small molecules with different pharmacologies onto a single antibody.

Ability to Incorporate Non-Natural Amino Acids.

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This enables us to move more rapidly to the clinic by eliminating master cell banking activities and significantly de-risks scale-up to manufacturing.

Our XpressCF ® Solution for Cytokine, ADCs, iADCs and Bispecific Antibody-Based Drug Therapeutics

As a result, we believe our technology enables new approaches to cytokine, ADCs, iADCs and bispecific antibody-based drug discovery, development and manufacturing.

Our XpressCF ® Solution for ADCs, iADCs, Bispecific ADCs, and ADC 2 Therapeutics

As a result, we believe our technology enables new approaches to ADCs, iADCs, bispecific ADCs, and ADC 2 drug discovery, development and manufacturing.

Key attributes are:

Homogeneous Design.

Our XpressCF+ ®TM platform enables precise and specific placement of non-natural amino acids in defined numbers and positions within our engineered proteins.

Our XpressCF+ ® platform enables precise and specific placement of non-natural amino acids in defined numbers and positions within our engineered proteins.

These non-natural amino acids then serve as highly stable attachment sites, also known as conjugation sites, for chemical functional groups.

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Experimentally Defined Structure-Activity Relationships .

Our cell-free technology enables rational design of protein therapeutics through a rapid, reiterative process that experimentally defines structure-activity relationship for cytokine-based therapeutics, ADCs, iADCs and bispecific antibodies.

This approach allows us to explore a wide variety of structural features and formats in parallel as we optimize therapeutic candidates.

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This design flexibility is also an important aspect of our discovery approach to other protein therapeutics.

For example, we are able to make and directly compare a variety of pairings and structural formats for our immuno-oncology bispecific antibody and bispecific T cell-engager programs.

This allows us to identify antibody pairs and formats with the best binding properties, spatial orientations and structural stability to create the optimal balance of therapeutic activity and safety.

Rapid and Efficient Transition from Discovery to the Clinic.

Protein therapeutics can encounter obstacles, or even fail, during the transition from research-grade cell lines to cGMP cell lines appropriate for clinical development and commercialization.

Our XpressCF ® platform can rapidly produce different protein types from a single proprietary extract, which can be scaled for discovery, development and ultimately, we believe, commercialization of cytokine-based immuno-oncology therapeutics, ADCs, iADCs and bispecific antibodies and bispecific T cell-engagers.

Accordingly, we use our XpressCF ® platform to discover and develop cancer therapeutics by empirically determining the optimum structure-activity relationships for cytokine-based immuno-oncology therapeutics, ADCs, iADCs, bispecific antibodies, and transitioning those products to cGMP compliant manufacturing.

The following chart illustrates the applicability of these attributes across the range of modalities we are developing.

XpressCF ® Attributes for Various Therapeutic Modalities

XpressCF ® Attribute

Bispecific I/O, Bispecific ADCs

and Bispecific T cell-engagers

Cytokine-based

Homogeneous Design

Stable, site-specific attachment of

chemical functionality

Experimentally Defined Structure-

Activity Relationships

Rapid, direct comparison of a wide

variety of protein variants

Rapid and Efficient Transition from

Discovery to the Clinic

Single-source scalability from discovery

to clinical / commercial

Our Collaborations Demonstrate our Capabilities

For example, we are able to make and directly compare a variety of pairings and structural formats for our ADC molecules to ensure that we have optimized sites of conjugation, the number of payloads on each antibody (DAR) and linker chemistry.

We have examples where changing just one of these parameters can significantly impact the safety, efficacy and stability of the ADC.

Efficient Transition from Research Scale to Development Scale Protein Production.

Protein therapeutics can encounter obstacles, or even fail, during the transition from research cell lines to cGMP cell lines appropriate for clinical development and commercialization.

Manufacturable Dual Conjugations.

Our XpressCF+ ® platform allows us to manufacture antibodies that contain two different non-natural amino acids that are substrates for mutually orthogonal site-specific conjugation reactions.

This advantage permits dual conjugation, resulting in homogenous iADC or ADC 2 dual conjugate molecules with two different precisely placed payloads.

Accordingly, we use our XpressCF ® platform to discover and develop cancer therapeutics by empirically determining the optimum structure-activity relationships for cytokine-based immuno-oncology therapeutics, ADCs, iADCs, bispecific ADCs and ADC 2 s and transitioning those products to cGMP compliant manufacturing.

Our Collaborations Validate Our Technology

Our XpressCF ® platform has garnered the attention of leading pharmaceutical and biopharmaceutical companies and resulted in collaborations to discover and develop novel therapeutics.

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Merck Programs.

We have granted Merck the right to develop two cytokine derivative candidate molecules.

We have granted Merck the right to develop MK-1484, a selective IL-2 agonist in clinical studies as a monotherapy and in combination with pembrolizumab for the treatment of solid tumors.

BMS Programs.

We have granted BMS the right to develop a novel ADC therapeutic directed against the target BCMA, known as CC-99712, which is currently under investigation in a Phase 1 trial focused on patients with relapsed and refractory multiple myeloma.

We have granted BMS the right to develop CC-99712, a novel ADC therapeutic directed against the target BCMA, which is currently under investigation for the treatment of relapsed and refractory multiple myeloma.

EMD Serono Programs.

We have granted EMD Serono the right to develop the novel bispecific ADC targeting EGFR and MUC1, known as M1231, which is currently under investigation for the treatment of solid tumors, including metastatic non-small cell lung cancer and esophageal squamous cell carcinoma in a Phase 1 trial.

We have granted EMD Serono the right to develop the novel bispecific ADC targeting EGFR and MUC1, known as M1231, for the treatment of solid tumors.

Astellas Collaboration.

We have entered into a collaboration and license agreement with Astellas for the discovery and development of immunostimulatory antibody-drug conjugates for up to three biological targets.

Vaxcyte Relationship.

We have granted Vaxcyte the right to discover and develop vaccines for the prophylaxis and treatment of infectious diseases.

Vaxcyte’s IND for its lead product candidate, a 24-valent pneumococcal conjugate vaccine, was cleared by the FDA in January 2022.

Vaxcyte’s most advanced product candidate is VAX-24, a 24-valent pneumococcal conjugate vaccine candidate under investigation for the prevention of invasive pneumococcal disease in adults.

In addition, we have granted Vaxcyte an option to obtain development and manufacturing rights for XtractCF ® that, when exercised, would grant Vaxcyte the right to make and source our cell-free extract for research, development, and manufacture of vaccines for the prophylaxis and treatment of infectious disease.

Tasly Relationship.

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Our current product candidates and Discovery and Preclinical stage programs, all based on our proprietary XpressCF ® platform, are summarized in the chart below:

(1) We have granted Tasly an exclusive license to the right to develop and commercialize STRO-002 in Greater China.

(2) We have granted BioNova an option to exclusively license the right to develop and commercialize STRO-001 in Greater China.

(3) EMD Serono is the biopharmaceutical business of Merck KGaA, Darmstadt Germany in the US.

(4) Cytokine derivative program with Merck includes two molecules derived from one undisclosed target.

(5) We are eligible to receive 4% royalties on net sales of VAX-24.

(1) EMD Serono is the biopharmaceutical business of Merck KGaA, Darmstadt Germany in the U.S.

Our Product Candidates

STRO-001, an ADC Directed Against the Cancer Target CD74

We are developing STRO-001, an optimally designed ADC directed against the cancer target CD74, for multiple myeloma and NHL.

STRO-001 was designed and optimized for maximal therapeutic index by placing linker-warheads at specific locations within the antibody using our proprietary XpressCF+ ®TM platform.

We are currently enrolling patients in a STRO-001 Phase 1 trial and presented updated data in December 2020.

Based on such reported data, STRO-001 has been generally well-tolerated and no ocular toxicity signals have been observed, with no patients receiving prophylactic corticosteroid eye drops.

Dose escalation in the STRO-001 Phase 1 trial is continuing, and the maximum tolerated dose has not yet been reached.

We expect to establish a recommended Phase 2 dose in 2022 and thereafter may begin the dose expansion portion of the Phase 1 trial.

In October 2018, we were granted Orphan Drug Designation by the FDA, for STRO-001 for the treatment of multiple myeloma.

In October 2021, we entered into the BioNova Option Agreement.

CD74 Overview and Current Limitations

CD74 is a transmembrane glycoprotein, or a protein with an attached sugar that spans the inside and outside of a cell.

While normal tissues appear to have minimal CD74 expression levels, CD74 is an important B cell target for multiple myelomas and lymphomas.

CD74 is expressed in approximately 90% of B cell cancers, including multiple myeloma and lymphoma.

Currently, there are no approved therapeutics that specifically target CD74 for treatment of B cell malignancies.

We believe earlier ADCs being developed against the target CD74 were ineffective either because they failed to achieve sufficient killing of malignant B cells or they were unable to achieve a sufficient therapeutic benefit before toxicities limited further dose escalations.

B Cell Malignancies Overview and Current Limitations

B cell malignancy tumor subtypes include multiple myeloma and NHL, which includes mantle cell lymphoma, diffuse large B cell lymphoma, or DLBCL, and follicular lymphoma.

In the United States alone in 2017, the prevalence of multiple myeloma and NHL was estimated at more than 800,000 cases, and the American Cancer Society estimated that there would be more than 116,000 new cases of multiple myeloma and NHL in 2021.

Although several therapeutics have recently been approved for the treatment of specific B cell malignancies, including immunotherapies, targeted kinase inhibitors, ADC and CAR-T cell therapies, unmet need persists.

Many of these therapeutics are typically used in combination with other agents to provide the most potent anti-cancer effect.

While these new therapies have demonstrated improvements in survival, the majority of these patients ultimately relapse during treatment and some experience a resistance to therapy.

Our Solution, STRO-001

Our first internally developed product candidate is STRO-001, which we believe has the potential to be a first-in-class and best-in-class ADC directed against the cancer target CD74, an antigen that is highly expressed in many B cell malignancies and is an attractive target for an ADC therapeutic, given its rapid internalization by the cell.

STRO-001 is an ADC targeting the CD74 protein antigen that was developed using our proprietary XpressCF ® and XpressCF+ ® platforms.

STRO-001 is composed of an antibody stably conjugated to a highly potent cytotoxic drug, a maytansinoid derivative, at two specific sites on the antibody using a non-cleavable linker.

STRO-001 degrades inside of tumor cells to release very potent intracellular catabolites whose hydrophilic nature results in poor permeability into surrounding cells.

We believe this decreases the potential of off-target effect in normal tissues.

From a safety perspective, we designed STRO-001 to have an optimal potency to toxicity ratio.

We rationally selected a homogeneous ADC with a drug-antibody ratio, or DAR, of two.

Heterogeneous ADCs typically have DARs that range from zero to eight, with lower DARs generally being associated with less potency and higher DARs generally being associated with a negative impact on pharmacokinetics and toxicity.

We chose a DAR of two after demonstrating that DARs of four or six did not increase the efficacy of STRO-001.

In October 2018, we were granted orphan drug designation by the FDA, for STRO-001 for the treatment of multiple myeloma.

Phase 1 Clinical Trial

The Phase 1 trial for STRO-001 is an open-label study that is evaluating STRO-001 as a monotherapy for patients with multiple myeloma and NHL.

The trial is being conducted in two parts:

dose escalation and dose expansion.

The primary objectives of the trial are to determine the safety and tolerability profile of STRO-001, determine the recommended Phase 2 dose and interval and evaluate preliminary anti-tumor activity.

The secondary objectives are to characterize the human pharmacokinetics of STRO-001 and additional safety, tolerability and efficacy measures.

Our Phase 1 trial of STRO-001 is enrolling adult patients with advanced and/or refractory multiple myeloma and NHL (including DLBCL, mantle cell lymphoma and follicular lymphoma) who are refractory to, or intolerant of, all established therapies known to provide clinical benefit for their condition.

Multiple myeloma and NHL patients are being enrolled in two separate dose escalation cohorts, starting initially with an accelerated dose titration design.

We estimate that there will be approximately 35-40 patients in each cohort.

Treatment is currently scheduled on day one of a 21-day cycle.

After the recommended Phase 2 dose level is determined, patients could be enrolled in up to four dose expansion cohorts (myeloma, DLBCL, mantle cell lymphoma and follicular lymphoma) if anti-tumor activity is observed during the dose escalation phase.

We may enroll up to 40 patients in each of the four dose expansion cohorts.

We submitted our IND for STRO-001 in December 2017 and the first patient was dosed in April 2018.

In October 2018, we were granted Orphan Drug Designation by the FDA for STRO-001 for the treatment of multiple myeloma.

In December 2020, we reported data from the NHL cohort from the dose escalation portion of the Phase 1 trial as of October 30, 2020:

Most (90%) treatment emergent adverse events were Grade 1 or 2 events of nausea, fatigue, chills, anemia, headache, dyspnea, abdominal pain, vomiting, decreased appetite and pyrexia, and no ocular or neuropathy toxicity signals have been observed.

Subsequent to a previously announced protocol amendment in 2019 requiring pre-treatment screening imaging for patients at risk for thromboses, no thromboembolic events have been observed.

In the seven patients with diffuse large B-cell lymphoma, one complete response and two partial responses were observed.

Out of other NHL types, two patients with follicular lymphoma had stable disease, of which one is still on treatment at nine weeks.

One patient with marginal zone lymphoma had stable disease and is still on treatment at 39 weeks.

In addition, the maximum tolerated dose was not reached at 4.2 mg/kg.

Active enrollment in the NHL cohort continues at the 5.0 mg/kg dose level and additional higher dose levels may be explored.

The maximum tolerated dose for the multiple myeloma dose escalation cohort has not been reached.

Active enrollment in that cohort continues at the 5.0 mg/kg dose level and additional higher dose levels may be explored.

The trial, registered with clinicaltrials.gov identifier NCT03424603, continues to enroll patients in dose escalation in both multiple myeloma and NHL cohorts.

We expect to determine the recommended Phase 2 dose for STRO-001 by the end of 2022.

In October 2021, we entered into the BioNova Option Agreement to confer BioNova the option to obtain exclusive rights to develop and commercialize STRO-001 in Greater China.

BioNova will pursue the clinical development, regulatory approval, and commercialization of STRO-001 in multiple indications, including NHL, multiple myeloma, and leukemia in the licensed territory.

We will retain development and commercial rights of STRO-001 globally outside of Greater China, including the United States.

STRO-002, an ADC Directed Against the Target Folate Receptor-Alpha (FolRα)

We are developing STRO-002, an optimally designed ADC directed against the cancer target FolRα, initially targeted for ovarian and endometrial cancers.

STRO-002 was designed and optimized for an improved therapeutic index by placing a precise number of linker-warheads at four specific locations within the antibody using our proprietary XpressCF+ ®TM platform.

We began enrolling patients in a STRO-002 Phase 1 trial focused on ovarian and endometrial cancers in March 2019 and presented updated dose-escalation data in December 2020 and May 2021.

Based on such reported data, STRO-002 exhibited a manageable safety profile and promising preliminary efficacy data.

Dose escalation in the STRO-002 Phase 1 trial has been fully enrolled and the dose-expansion portion of the trial is ongoing to assess the efficacy, safety and tolerability of STRO-002 at dose levels of 4.3 and 5.2 mg/kg.

Luveltamab tazevibulin (luvelta), an ADC Directed Against the Target Folate Receptor-Alpha (FolRα)

We are developing luveltamab tazevibulin, or luvelta, an optimally designed ADC directed against the cancer target FolRα, initially focused on ovarian and endometrial cancers.

Luvelta was designed and optimized for an improved therapeutic index by placing a precise number of linker-warheads at four specific locations within the antibody using our proprietary XpressCF+ ® platform.

Phase 1 trial enrollment, focused on ovarian and endometrial cancers, began in March 2019, with updated dose-escalation data presented in December 2020 and May 2021.

We reported initial dose-expansion data in January 2022 and a near-final dataset in January 2023.

Based on such reported data, Luvelta exhibited a manageable safety profile and promising preliminary efficacy data.

Dose escalation in the Phase 1 trial has been fully enrolled and the dose-expansion portion of the trial is ongoing to assess the efficacy, safety, and tolerability of luvelta at dose levels of 4.3 and 5.2 mg/kg.

For the dose-expansion portion of the Phase 1 trial, we dosed the first patient in January 2021 and have enrolled less heavily pre-treated ovarian cancer patients.

We reported initial dose-expansion data in January 2022.

Based on the reported data, STRO-002 demonstrated a manageable safety profile and promising preliminary efficacy data.

Additionally, a STRO-002 combination cohort in ovarian cancer, assessing the combination of STRO-002 with bevacizumab, opened for enrollment in December 2021, and an expansion cohort for FolRα-selected endometrial cancer opened and began enrolling patients in the fourth quarter of 2021.

In August 2021, we were granted Fast Track designation for STRO-002 by the FDA for the treatment of patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior lines of systemic therapy.

In December 2021, we entered into a collaboration and exclusive license agreement with Tasly to develop and commercialize STRO-002 in Greater China.

is a cell-surface glycoprotein, which is believed to be important for supporting DNA synthesis in rapidly dividing cancer cells.

exhibits limited expression and distribution in normal tissues.

High levels of FolRα

have been found in multiple cancer types, including epithelial ovarian cancer, endometrial adenocarcinoma, triple negative breast cancer and non-small cell lung cancer.

Expression appears to correlate with disease progression in ovarian cancer and continues to be expressed following chemotherapy treatment.

Additionally, a combination cohort in ovarian cancer, assessing the combination of luvelta with bevacizumab, opened for enrollment in December 2021, and an expansion cohort for FolRa-selected endometrial cancer opened and began enrolling patients in the fourth quarter of 2021.

An expansion cohort assessing the effects of administration of prophylactic pegfilgrastim in combination with luvelta opened for enrollment in the second quarter of 2022;

interim results from this cohort were also presented in January 2023.

In August 2021, we were granted Fast Track designation for luvelta by the FDA for the treatment of patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior lines of systemic therapy.

In December 2021, we entered into a collaboration and exclusive license agreement with Tasly to develop and commercialize luvelta in Greater China.

Luvelta has been provided through compassionate use to pediatric patients with relapsed/refractory CBF/GLIS AML, which data were presented at ASH 2022.

The data showed that luvelta was well tolerated as a monotherapy agent and in combination with standard cancer therapies.

In December 2022, luvelta was granted Orphan Drug Designation by the FDA for this pediatric indication.

Ovarian Cancer Overview

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In the United States alone, the American Cancer Society estimates that 19,000 new cases of ovarian cancer would be diagnosed in 2023, and approximately 13,270 women would die of this disease.

Given that early stages of the disease cause minimal, nonspecific symptoms or is asymptomatic, approximately 75% of patients with ovarian cancer are diagnosed are stage III and IV, for which the prognosis is poor.

Given that early stages of the disease cause minimal, nonspecific symptoms or are asymptomatic, approximately 75% of patients with ovarian cancer are diagnosed as stage III and IV, for which the prognosis is poor.

Standard pre- or post-operative chemotherapy for ovarian cancer is combination therapy with a platinum compound and a taxane, for example, carboplatin and paclitaxel, with or without bevacizumab which achieves a complete or partial response in between 70% to 80% of patients.

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There is also a significant unmet need in the treatment of recurrent or metastatic endometrial cancer.

In the United States alone, the American Cancer Society estimated that there would be more than 66,000 new cases of endometrial cancer in 2021, and that approximately 13,000 women would die of this disease.

In the United States alone, the American Cancer Society estimated 66,000 new cases of endometrial cancer in 2023, and that approximately 13,000 women would die of this disease.

First-line treatment for stage III/IV disease is commonly paclitaxel/carboplatin.

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With the lack of available therapies for patients who progress after standard of care therapies, long-term survival prospects are poor and novel treatments offering even a modest improvement in progression-free survival or overall survival may be considered for expedited regulatory approval.

Pediatric AML CBFA2T3-GLIS2 (CBF/GLIS) Phenotype Overview

There remains a significant unmet need in the treatment of CBF/GLIS AML in pediatric patients.

The CBF/GLIS subtype of AML is a rare, aggressive form of AML that has never been found in adult AML patients, and typically affects pediatric patients with a median age of 1.5 years.

The prevalence of CBF/GLIS AML is 1%-3% in childhood AML, and in recent studies the incidence was determined to be 1.3%-1.8% of pediatric AML patients.

The prognosis for this disease is grim, with a 5-year overall survival of 15-30%.

The first-line treatment for this disease is chemotherapy with a goal of reducing disease burden to the point that the patient can receive a bone marrow transplant.

Patients who are refractory to primary chemotherapy or who relapse following bone marrow transplant have no additional treatment options and have very poor treatment outcomes.

Given the lack of treatment options for these patients, a novel treatment that offers an opportunity for these patients to become eligible for bone marrow transplantation may be considered for expedited regulatory review.

Limitations to Current FolRα-Targeted Therapeutics

There have been a number of folate- or FolRα-targeted therapies in development, including naked antibodies, small molecule drug conjugates, ADCs and T cell retargeting molecules.

There have been a number of FolRα-targeted therapies in development, including naked antibodies, small molecule drug conjugates, ADCs, and T cell retargeting molecules.

The most advanced clinically active agent targeting FolRα

to date has been Immunogen’s mirvetuximab soravtansine (IMGN853), an ADC composed of a FolRα-binding antibody linked to the tubulin-disrupting maytansinoid, DM4, via a cleavable linker.

Immunogen announced in December 2019 that the FDA has provided guidance for potential accelerated approval of its mirvetuximab soravtansine (mirvetuximab) monotherapy, demonstrating that FolRα

remains an attractive target.

In November 2021, Immunogen reported positive top-line data in its SORAYA trial evaluating the safety and efficacy of mirvetuximab soravtansine monotherapy in patients with high FRα-expressing platinum-resistant ovarian cancer who have been previously treated with Avastin ® (bevacizumab).

Mirvetuximab soravtansine is currently being evaluated in a Phase 3 randomized confirmatory trial, and in multiple combination studies.

Our Solution, STRO-002

STRO-002 is directed against the cancer target FolRα, which is highly expressed in multiple cancer types, including ovarian cancer and endometrial cancer.

This property, together with the highly restricted expression of FolRα

on normal tissues, make FolRα

to date has been Immunogen’s ELAHERE (mirvetuximab soravtansine IMGN853), an ADC composed of a FolRα-binding antibody linked to the tubulin-disrupting maytansinoid, DM4, via a cleavable linker.

In November 2022, the FDA granted accelerated approval to Immunogen for ELAHERE for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens.

Patients are selected for therapy based on an FDA-approved test that defines FRα-positivity by 2+ and/or 3+ IHC staining in ≥75% of tumor cells.

BMS and Eisai Co., Ltd., or Eisai, are also co-developing a FolRα-targeted ADC for the treatment of cancers, including ovarian cancers, identified as MORAb-202.

MORAb-202 is an ADC made from the anti-FolRα

antibody farletuzumab conjugated to an average of four eribulin molecules via a cleavable linker.

Public information about MORAb-202 development is limited, but a Phase II efficacy study of MORAb-202 was described as open and enrolling on the clinical trials.gov website in the fourth quarter of 2022.

Also, Elucida Oncology is developing a nanoparticle C’Dot drug conjugate targeting FolRα.

Our Solution, luveltamab tazevibulin (luvelta)

Luvelta targets FolRα, a surface protein with limited expression on normal tissue and overexpressed in multiple cancers, including ovarian cancer, which makes FolRα

a promising ADC approach.

STRO-002 employs a cleavable linker that releases a cytotoxic drug inside of tumor cells, while being stable and resistant to cleavage in general circulation.

Luvelta employs a cleavable linker that releases a cytotoxic drug inside tumor cells, while being stable and resistant to cleavage in general circulation.

The cytotoxic drug used is our proprietary hemiasterlin moiety.

From a safety perspective, we designed STRO-002 to have the optimal potency-to-safety ratio.

We rationally selected a homogenous ADC with an optimized DAR of four.

Based on preclinical findings, we believe our efficient homogeneous design of STRO-002 could provide anti-tumor activity, stability and safety with the potential to minimize off-target damage and improve clinical impact by reducing dose-limiting toxicities.

We believe an improved therapeutic index could differentiate STRO-002 from conventional technology for the treatment of ovarian cancer and endometrial cancer.

From a safety perspective, we designed luvelta to have what we believe to be the optimal potency-to-safety ratio.

We therefore rationally selected a homogenous ADC with an optimized DAR of four.

Based on preclinical findings, we believe our efficient homogeneous design of luvelta could provide anti-tumor activity, stability, and safety with the potential to minimize off-target damage and improve clinical benefit.

We believe an improved therapeutic index could differentiate luvelta from conventional technology for the treatment of ovarian cancer and endometrial cancer.

To test this, we have created a benchmark FolRα-targeting surrogate molecule based on conventional technology that has a heterogeneous ADC, with a similar DAR utilizing a DM4 linker-warhead.

We have tested this benchmark molecule against STRO-002 in multiple preclinical models.

However, additional preclinical and clinical testing will be needed to determine the safety and efficacy of STRO-002 and to obtain regulatory approval, if ever.

STRO-002 may not ultimately provide a greater therapeutic benefit than the current standard of care.

We have tested this benchmark molecule against luvelta in multiple preclinical models.

However, additional preclinical and clinical testing will be needed to determine the safety and efficacy of luvelta and to obtain regulatory approval, if ever obtained.

Clinical Development Plan

Our first Phase 1 trial for STRO-002 is an open-label study evaluating STRO-002 as a monotherapy for patients with ovarian and endometrial cancers.

Our first Phase 1 trial for luvelta is an open-label study evaluating luvelta as a monotherapy for patients with ovarian and endometrial cancers.

This trial is being conducted in two-parts, dose escalation and dose expansion.

We began enrolling ovarian cancer patients in March 2019, with updated data for the dose escalation cohort reported in December 2020 and May 2021.

The primary objectives of the STRO-002 clinical trial are to determine the safety and tolerability profile, to define the recommended Phase 2 dose level and interval and to evaluate preliminary anti-tumor activity.

Our secondary objectives are to characterize the human pharmacokinetics and additional safety, tolerability and efficacy measures.

The primary objectives of the clinical trial are to determine the safety and tolerability profile, to define the recommended Phase 2 dose level and interval, and to evaluate preliminary anti-tumor activity.

Our secondary objectives are to characterize human pharmacokinetics and additional safety, tolerability, and efficacy measures.

We initially enrolled adult patients with advanced and/or refractory ovarian cancer, for whom no suitable treatment exists.

These patients are considered to have incurable disease and need repeated courses of life-prolonging and palliative treatment.

The initial STRO-002 Phase 1 trial enrolled ovarian cancer patients regardless of their FolRα

The initial Phase 1 trial enrolled ovarian cancer patients regardless of their FolRα

expression levels.

These ovarian cancer patients were enrolled in a dose escalation cohort, with STRO-002 administered on day one of a 21-day cycle.

Since anti-tumor activity was observed during the dose escalation portion of the Phase 1 trial, we initiated enrollment of patients in the dose expansion portion of this clinical study in January 2021 and are treating less heavily pre-treated ovarian cancer patients.

Enrollment of the dose-expansion portion of the Phase 1 study is complete and the study is currently ongoing.

These ovarian cancer patients were enrolled in a dose escalation cohort, with luvelta administered on day one of a 21-day cycle.

Since anti-tumor activity was observed during the fully enrolled dose escalation portion of the Phase 1 trial, we initiated enrollment of patients in the dose expansion portion of this clinical study in January 2021 and are treating less heavily pre-treated ovarian cancer patients.

The dose expansion portion of this Phase 1 study of luvelta is fully enrolled and currently ongoing.

In May 2021, we announced updated data from the dose-escalation portion of our ongoing Phase 1 clinical trial of STRO-002 in patients with ovarian cancer.

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At the data cutoff of April 23, 2021, results out of 31 evaluable patients included:

10 patients (32%) met RECIST criteria for response, of which, one patient achieved a complete response and nine patients achieved a partial response (four confirmed partial responses and five unconfirmed partial responses).

For the five confirmed responders (1 complete response, or CR, and 4 confirmed partial responses, or cPRs), the median duration of response, or DOR, was 5.8 months (95% CI:

10 patients (32%) met RECIST criteria for response, of which, one patient achieved a complete response, or CR, and nine patients achieved a partial response (four confirmed partial responses and five unconfirmed partial responses).

For the five confirmed responders (1 CR and 4 confirmed partial responses), the median duration of response, or DOR, was 5.8 months (95% CI:

2.0, not evaluable).

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For the dose-expansion portion, we dosed the first patient in January 2021 and are treating less heavily pre-treated ovarian cancer patients.

We reported initial dose-expansion data in January 2022.

The dose-expansion cohort for ovarian cancer enrolled 44 patients, who had experienced up to three prior lines of therapy.

As of the interim data cutoff date of November 8, 2021, 43 patients had been randomized into dose levels starting at 4.3 mg/kg and 5.2 mg/kg, and one patient had not yet been dosed.

We reported initial dose-expansion data in January 2022 and preliminary final data in January 2023.

We also initiated an exploratory dose expansion cohort of 15 patients to assess the safety of treatment with luvelta at 5.2 mg/kg in combination with prophylactic pegfilgrastim, and interim results from this cohort were also presented in January 2023.

The dose-expansion cohort for ovarian cancer fully enrolled 44 patients, who had experienced up to three prior lines of therapy and were randomized into dose levels starting at 4.3 mg/kg (N=23) and 5.2 mg/kg (n=21).

81% of the patients were platinum-resistant, and 66% and 82% of the patients had been treated previously with bevacizumab and PARP inhibitors, respectively.

Of the 43 patients, 33 had at least one post-baseline scan, and therefore were evaluable for RECIST v1.1 responses.

As of the interim data cutoff date, the Best Overall Response for evaluable patients were as follows (N=33):

Seven patients had achieved partial responses, or PR, which were confirmed with at least two post-baseline scans.

Five patients had unconfirmed partial responses, or PRus, based on having received only one post-baseline scan as of the interim data cutoff date.

Their next scheduled scan, subsequent to the interim data cutoff date, revealed the following:

Four PRs were confirmed and one patient was in stable disease, or SD.

An Objective Response Rate, or ORR, of 33% (11 confirmed PRs out of 33 patients) was demonstrated in all evaluable patients, unenriched for FolRα-expression levels at both dose levels.

14 total patients experienced SD and 8 patients had progressive disease, or PD.

Dose response was observed, with an ORR of 47% (8 PRs out of 17 patients) for patients who started at the 5.2 mg/kg dose level, unenriched for biomarker status.

The patients were also assessed for FolRα

Higher FolRα

expression levels calculated using tumor proportion scores, or TPS, correlated with higher response rates.

We have identified TPS as a potentially appropriate scoring algorithm for STRO-002 with respect to the biomarker enrichment strategy.

Based on an exploratory cut-off of TPS > 25%, we observed a 40% ORR (10 PRs out of 25 patients) irrespective of initial dose.

TPS <=25% demonstrated a 13% ORR.

In a limited number of patients with TPS > 25% and who were treated with an initial dose of 5.2 mg/kg, we further observed a 53.8% ORR (7 PRs out of 13 patients).

Based on the population statistics in our Phase 1 trial, an enrichment approach of TPS > 25% FolRα

expression may enable treatment of about 70% of the advanced ovarian cancer patient population.

Safety signals from the 43 safety evaluable patients, at the 5.2 mg/kg and 4.3 mg/kg starting dose levels, were consistent with data from the dose-escalation cohort, including:

No qualitatively new safety signals were observed in the dose-expansion cohort, including the absence of keratopathy.

85.5% TEAEs were Grade 1-2.

Neutropenia was the leading TEAE, resulting in treatment delay or dose reduction.

We have identified TPS as a potentially appropriate scoring algorithm for luvelta with respect to the biomarker enrichment strategy.

Of the 44 patients in this cohort, 9 had a TPS score of less than or equal to 25%, while 35 had a TPS score of greater than 25%.

Of these 35 patients, as of the data cutoff date of November 8, 2022, 32 had at least one post-baseline scan, and therefore were evaluable for RECIST v1.1 responses.

The results demonstrated that luvelta provided substantial clinical benefit in FolRα-selected patients, defined by TPS of >25%, with a 37.5% overall response rate (ORR), median DOR of 5.5 months, and median PFS of 6.1 months, regardless of starting dose.

Results also demonstrated the higher starting dose of 5.2 mg/kg provided greater patient benefit compared to the lower starting dose of 4.3mg/kg.

FolRα-selected patients account for approximately 80% of the patient population in advanced ovarian cancer, as represented in the patient stratification in the Phase 1 study.

In particular:

Patients who were FolRα-selected, defined by TPS >25%, regardless of starting dose, demonstrated an ORR of 37.5% (n=32) with a median DOR of 5.5 months (n=12) and a median PFS of 6.1 months (n=35).

Estimated targeted luvelta patient population is approximately 80% of advanced ovarian cancer patients based on pooled Phase 1 biomarker data.

Luvelta demonstrated a FolRα-dependent response, with patients who were unselected for FolRα

(TPS ≤25%) demonstrating an 11.1% ORR (n=9) with a median DOR of 2.9 months (n=1) and a median PFS of 3.8 months (n=9).

FolRα-selected patients given the 4.3 mg/kg dose of luvelta demonstrated an ORR of 31.3% (n=16), a median DOR of 13 months (n=5) and a median PFS of 6.1 months (n=19).

Luvelta, when given to FolRα-selected patients at a starting dose of 5.2 mg/kg, provided greater patient benefit than a starting dose of 4.3 mg/kg, with the 5.2 mg/kg dose of luvelta demonstrating an ORR of 43.8% (n=16), a median DOR of 5.4 months (n=7) and a median PFS of 6.6 months (n=16)

Safety signals from the 44 patients at the 5.2 mg/kg and 4.3 mg/kg starting dose levels, were consistent with data from the dose-escalation cohort, including:

No qualitatively new safety signals were observed in the dose-expansion cohort, including the absence of meaningful ocular or lung toxicity signals or complications.

Neutropenia was the leading TEAE that resulted in a treatment delay or a dose reduction.

The majority of the cases of neutropenia were generally asymptomatic and resolved with a one-week dose delay or, in other cases, with standard medical treatment, including the use of G-CSF.

Arthralgia was the second most common Grade 3 or higher, or Grade 3+, TEAE and second most common TEAE leading to dose reduction.

There were limited observed cases of febrile neutropenia, including one Grade 5 event at the 5.2 mg/kg starting dose level and one Grade 3 event at the 4.3 mg/kg starting dose level.

The trial protocol was subsequently updated to require dose reduction for Grade 4 neutropenia.

Data from the STRO-002 dose-expansion cohort are expected to provide further information to inform regulatory discussions and a global registration strategy.

Additionally, a Phase 1 trial to assess the combination of STRO-002 and bevacizumab for treatment of ovari an cancer was opened for enrollment in December 2021.

We expect to present initial results from this study in the first half of 2023.

Moreover, an expansion cohort for FolRα-selected endometrial cancer began enrolling patients in the fourth quarter of 2021.

We expect to present initial results from this study in the first half of 2023.

Finally, we plan to initiate a pilot study to assess STRO-002 for the treatment of NSCLC and other non-gynecologic cancers in the second half of 2022.

In 2022 we initiated an exploratory cohort, or cohort C, of 15 patients to assess the safety of treatment with luvelta at 5.2 mg/kg in combination with prophylactic pegfilgrastim and presented preliminary data from ten patients from this cohort in January 2023.

Early results from these initial 10 patients in cohort C, when compared to patients who were not given prophylactic pegfilgrastim in the dose-expansion cohort at the 5.2 mg/kg dose (n=21) demonstrated substantial reductions in Grade 3+ neutropenia and instances of dose delays.

In particular:

Grade 3+ neutropenia was reduced from 66.7% to 10.0%, resulting in an 85.0% decrease in Grade 3+ neutropenia rates at the first cycle of luvelta (p=0.006).

Instances of dose delays at the second cycle of luvelta were reduced by 60.6% (p=0.021).

Additionally, we opened for enrollment a Phase 1 trial to assess the combination of STRO-002 and bevacizumab for treatment of ovarian cancer in December 2021 and began enrolling patients in an expansion cohort for FolRα-selected endometrial cancer in the fourth quarter of 2021.

We expect to present initial results from each of these studies in the second half of 2023.

Further, we plan to submit an IND for the treatment of NSCLC with luvelta by the end of 2023 or in early 2024.

We are also seeking to develop luvelta for the treatment of CBF/GLIS AML in pediatric patients.

Initial access to luvelta in this indication has been provided through compassionate use.

Initial data on the anti-leukemic activity of luvelta in 17 pediatric patients with relapsed/refractory CBF/GLIS AML was presented at ASH 2022.

The ASH 2022 presentation included results from 17 patients treated with luvelta that were relapsed or refractory to standard of care treatments.

The median age of the patients treated was two years old and the median number of prior therapies was two.

Eight of the patients had previously undergone a stem cell transplant (SCT).

Luvelta was well-tolerated as a monotherapy agent and in combination with standard of care therapies.

In the 17 patients treated, Best Overall Response (BOR) included eight patients with complete remission (CR), of which seven patients were minimal residual disease (MRD) negative.

47% of the patients achieved complete remission and 53% of the patients achieved partial response or stable disease.

Responders were observed in varying contexts, including those with or without prior stem cell transplant and in monotherapy or in combination with cytotoxic therapy.

We met with the FDA to discuss our clinical development plan for luvelta to treat pediatric CFB/GLIS AML in January 2023 and plan to submit an IND for this indication in the first half of 2023.

STRO-001, an ADC Directed Against the Cancer Target CD74

We are developing STRO-001, an optimally designed ADC directed against the cancer target CD74, for multiple myeloma and NHL.

STRO-001 was designed and optimized for maximal therapeutic index by placing linker-warheads at specific locations within the antibody using our proprietary XpressCF+ ® platform.

We have completed enrollment for STRO-001 in a Phase 1 trial for multiple myeloma and NHL for which we reported updated data in December 2020.

Based on such reported data, STRO-001 has been generally well-tolerated and no ocular toxicity signals have been observed, with no patients receiving prophylactic corticosteroid eye drops.

The maximum tolerated dose of STRO-001 has been identified.

We have paused further enrollment of patients in the STRO-001 Phase 1 trial following identification of the maximum tolerated dose.

In October 2018, we were granted Orphan Drug Designation by the FDA for STRO-001 for the treatment of multiple myeloma.

In October 2021, we entered into the BioNova Option Agreement.

CD74 Overview and Current Limitations

CD74 is a transmembrane glycoprotein, or a protein with an attached sugar that spans the inside and outside of a cell.

While normal tissues appear to have minimal CD74 expression levels, CD74 is an important B cell target for multiple myelomas and lymphomas.

CD74 is expressed in approximately 90% of B cell cancers, including multiple myeloma and lymphoma.

Currently, there are no approved therapeutics that specifically target CD74 for treatment of B cell malignancies.

We believe earlier ADCs being developed against the target CD74 were ineffective either because

they failed to achieve sufficient killing of malignant B cells or they were unable to achieve a sufficient therapeutic benefit before toxicities limited further dose escalations.

B Cell Malignancies Overview and Current Limitations

B cell malignancy tumor subtypes include multiple myeloma and NHL, which includes mantle cell lymphoma, diffuse large B cell lymphoma, or DLBCL, and follicular lymphoma.

In the United States alone in 2019, the prevalence of multiple myeloma and NHL was estimated at more than 920,000 cases, and the American Cancer Society estimated that there would be more than 116,000 new cases of multiple myeloma and NHL in 2023.

Many of these therapeutics are typically used in combination with other agents to provide the most potent anti-cancer effect.

While these new therapies have demonstrated improvements in survival, the majority of these patients ultimately relapse during treatment and some experience a resistance to therapy.

Our Solution, STRO-001

STRO-001 is an ADC targeting the CD74 protein antigen that was developed using our proprietary XpressCF ® and XpressCF+ ® platforms.

STRO-001 is composed of an antibody stably conjugated to a highly potent cytotoxic drug, a maytansinoid derivative, at two specific sites on the antibody using a non-cleavable linker.

STRO-001 degrades inside of tumor cells to release very potent intracellular catabolites whose hydrophilic nature results in poor permeability into surrounding cells.

We believe this decreases the potential of off-target effect in normal tissues.

From a safety perspective, we designed STRO-001 to have an optimal potency to toxicity ratio.

We rationally selected a homogeneous ADC with a drug-antibody ratio, or DAR, of two.

We chose a DAR of two after demonstrating that DARs of four or six did not increase the preclinical efficacy of STRO-001.

In October 2018, we were granted orphan drug designation by the FDA, for STRO-001 for the treatment of multiple myeloma.

Phase 1 Clinical Trial

The Phase 1 trial for STRO-001 is an open-label study that is evaluating STRO-001 as a monotherapy for patients with multiple myeloma and NHL.

The trial is being conducted in two parts:

dose escalation and dose expansion.

The primary objectives of the trial are to determine the safety and tolerability profile of STRO-001, determine the recommended Phase 2 dose and interval and evaluate preliminary anti-tumor activity.

The secondary objectives are to characterize the human pharmacokinetics of STRO-001 and additional safety, tolerability and efficacy measures.

Our Phase 1 trial of STRO-001 has been enrolling adult patients with advanced and/or refractory multiple myeloma and NHL (including DLBCL, mantle cell lymphoma and follicular lymphoma) who are refractory to, or intolerant of, all established therapies known to provide clinical benefit for their condition.

Multiple myeloma and NHL patients have been enrolled in two separate dose escalation cohorts, starting initially with an accelerated dose titration design.