What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2024-05-16 compared with 2023-05-18 · 215 added, 172 removed, 479 unchanged (45% of the section changed)

We are a clinical-stage biotechnology company committed to applying our leading expertise in the field of oncolytic immunotherapy to transform the lives of cancer patients through our novel tumor-directed oncolytic immunotherapies.

Our proprietary tumor-directed oncolytic immunotherapy product candidates are designed and intended to maximally activate the immune system against cancer.

Our proprietary oncolytic immunotherapy product candidates are designed and intended to maximally activate the immune system against cancer.

Oncolytic immunotherapy is an emerging drug class, which we intend to establish as the second cornerstone of immune-based cancer treatments, alongside checkpoint blockade.

Oncolytic immunotherapy exploits the ability of certain viruses to selectively replicate in and directly kill tumors, as well as induce a potent, patient-specific, anti-tumor immune response.

Our product candidates incorporate multiple mechanisms of action into a practical “off-the-shelf” approach that is intended to maximize the immune response against a patient’s cancer and to offer significant advantages over other approaches to inducing anti-tumor immunity, including personalized vaccine approaches.

We believe that the bundling of multiple approaches for the treatment of cancer into single therapies will increase clinical efficacy and simplify the development path of our product candidates, while also improving patient outcomes at a lower cost to the healthcare system than the use of multiple different drugs.

Our proprietary RPx platform is based on a proprietary, engineered strain of herpes simplex virus 1, or HSV-1, backbone with payloads added to maximize immunogenic cell death and the induction of a systemic anti-tumor immune response.

The RPx platform has a unique dual local and systemic mechanism of action, or MOA, consisting of direct selective virus-mediated killing of the tumor resulting in the release of tumor-derived antigens and altering of the tumor microenvironment, or TME, to ignite a strong and durable systemic response.

This MOA is expected to be synergistic with most established and experimental cancer treatment modalities, and, with an attractive safety profile, the RPx platform is expected to have the versatility to be developed alone or combined with a variety of other treatment options.

We currently have three RPx product candidates in our development pipeline, RP1 (vusolimogene oderparepvec), our lead product candidate, RP2 and RP3.

Although our fiscal year runs from April 1st - March 31st, our programs and program updates disclosed herein and elsewhere are reported on a calendar year basis.

Our product candidates incorporate multiple mechanisms into a practical “off-the-shelf” approach that is intended to maximize the immune response against a patient’s cancer and to offer significant advantages over other approaches to inducing anti-tumor immunity, including personalized vaccine approaches.

We believe that the bundling of multiple approaches for the treatment of cancer into single therapies may improve patient outcomes and simplify the development path of our product candidates.

Our proprietary RPx platform is based on a novel, engineered strain of herpes simplex virus 1, or HSV-1, backbone with payloads added to maximize immunogenic cell death and the induction of a systemic anti-tumor immune response.

Our RPx platform is intended to have unique dual local and systemic activity consisting of direct selective virus-mediated killing of the tumor resulting in the release of tumor-derived antigens and altering of the tumor microenvironment to ignite a strong and durable systemic response.

Our product candidates are expected to be synergistic with most established and experimental cancer treatment modalities, and, with an attractive safety profile our RPx platform is expected to have the versatility to be developed alone or combined with a variety of other treatment options.

We currently have three RPx product candidates in our portfolio, RP1 (vusolimogene oderparepvec), our lead product candidate, RP2 and RP3.

Although our fiscal year ends March 31st, our programs and program updates are reported on a calendar year basis.

We are conducting a number of clinical trials of RP1, both as a monotherapy and in combination with anti-PD-1 therapy, with a focus on establishing a major skin cancer franchise.

We have completed enrolling patients in a randomized, controlled Phase-2 clinical trial of RP1 with cutaneous squamous cell carcinoma, or CSCC, RP1’s lead indication, which is referred to herein as CERPASS or the CERPASS trial, under an agreement with our partner Regeneron Pharmaceuticals, Inc., or Regeneron.

CERPASS is a registration directed clinical trial evaluating RP1 in combination with cemiplimab, an anti-PD-1 therapy developed by Regeneron, versus cemiplimab alone.

Regeneron has granted to us a non-exclusive royalty-free license to cemiplimab for use in this trial, is supplying cemiplimab at no cost and funded one-half of the clinical trial costs up to the amount agreed in the first study plan.

CERPASS enrolled 211 patients with locally advanced or metastatic CSCC who are naïve to anti-PD1 therapy.

An additional 20 patients were also dosed with RP1 made at our in-house manufacturing facility.

The CERPASS protocol evaluates complete response, or CR rate, and overall response rate, or ORR, as its two independent primary efficacy endpoints as assessed by independent review, as well as duration of response, progression-free survival, or PFS, and overall survival, or OS, as secondary endpoints.

As previously reported, we met with the FDA in the first quarter and discussed the rationale for the changes to the study design we made in 2020 reducing the study size from 240 to 180 patients and adding CR as a dual independent primary endpoint (the study subsequently over enrolled with 211 patients randomized, as reported in November 2022).

No changes were made to the protocol as a result of the meeting.

As reported in February 2023, topline data from the CERPASS trial is expected to be announced in Q3 2023.

Assuming positive primary analysis data is generated, including demonstrating overall clinical benefit, we continue to expect to make a Biologics License Application submission for RP1 in Q1 2024.

We continue our collaboration with Bristol Myers Squibb Company, or BMS, under which BMS has granted us a non-exclusive, royalty-free license to, and is supplying at no cost, its anti-PD-1 therapy, nivolumab, for use in combination with RP1 in a multi-cohort Phase 1/2 clinical trial which is referred to herein as IGNYTE, or the IGNYTE trial.

Our leading clinical trial of RP1 is our IGNYTE trial, a multi-cohort Phase 1/2 clinical trial being conducted in collaboration with Bristol Myers Squibb Company, or BMS, under which BMS has granted us a non-exclusive, royalty-free license to, and is supplying at no cost, its anti-PD-1 therapy, nivolumab, for use in combination with RP1.

The leading tumor specific cohort in the IGNYTE trial is our registration directed Phase 2 expansion cohort enrolling patients with anti-PD-1 failed cutaneous melanoma who are being treated with RP1 in combination with nivolumab.

We are also continuing enrollment into the cohorts of patients with anti-PD-1 failed non-melanoma skin cancers, or NMSC, which includes patients with both naïve and anti-PD-1 failed disease, including CSCC.

We initiated the registration directed Phase 2 expansion cohort in the IGNYTE trial enrolling 125 patients with anti-PD-1 failed cutaneous melanoma after completing enrollment in a prior Phase 2 cohort in the same clinical trial of approximately 30 patients with melanoma, which demonstrated the tolerability and clinical activity of the combination of RP1 and nivolumab in patients with melanoma, including those who had failed prior anti-PD-1 when given alone or in combination with CTLA-4 blockade.

In March 2021, we held a Type B meeting with the FDA to discuss the design of the 125 patient expansion cohort in the IGNYTE trial.

In this meeting, the FDA expressed that while a randomized controlled clinical trial would always be preferred for registration purpose, that in this patient population with no clear standard of care, if the clinical data is sufficiently compelling then the data could be considered for submission by the FDA under the accelerated approval pathway.

The FDA also indicated that a randomized confirmatory trial would also be needed as is required under the accelerated approval pathway.

The design of the confirmatory trial is intended to be discussed with the FDA prior to a BLA submission.

In December 2022, we reported data from the first 75 patients with at least six months follow-up.

The data snapshot based on investigator response showed a 20% CR rate and a 36% ORR with activity across all disease stages and strong durability.

In January 2023, we completed target enrollment of 125 patients with patients in screening at that time continuing to be enrolled.

We completed enrollment in this cohort in March 2023, ultimately enrolling 141 patients.

Further updated data from the initial 75 patients is expected to be presented at the American Society of Clinical Oncology, or ASCO, in June 2023, and a data snapshot for all 141 patients, who will all have a minimum of 6 months follow-up, is expected in Q4 2023.

The data snapshot for all 141 patients with a minimum of 6 months follow-up will be evaluated for the potential to align a dual launch with CERPASS, assuming both indications for RP1 are timely approved, however, the per protocol primary analysis continues to be expected 12 months after enrollment of the last patient, March 2024, with topline data expected in Q2 2024.

We continue to enroll patients in our additional IGNYTE Phase-2 cohorts under our collaboration with BMS in which we are evaluating RP1 in combination with nivolumab.

In NMSC, enrollment in the anti-PD-1 naïve NMSC cohort has completed, included patients with cutaneous squamous cell carcinoma, or CSCC, basal cell carcinoma, or BCC, merkel cell carcinoma, or MCC, and angiosarcoma.

Updated data from the CSCC patients in the anti-PD-1 naïve NMSC cohort, presented in March 2022, continued to show nearly half of the patients achieving a complete response and nearly 65% achieving a complete or partial response.

We are currently enrolling an extension of the NMSC cohort of RP1 in combination with nivolumab in NMSC patients who have failed prior treatment with anti-PD(L)-1.

In March 2022, we reported initial data (N=12) from this extension cohort where responses had been observed in anti-PD(L)-1 failed CSCC, MCC and angiosarcoma tumors.

We believe the activity of RP1 combined with nivolumab in this anti-PD(L)-1 failed cohort represents a new potential therapeutic option for these patients and supports the broad potential for RP1 in anti-PD(L)-1 failed skin cancers beyond melanoma.

Recruitment remains ongoing, with a data update expected in Q3 2023.

We also have open for enrollment a Phase 1b/2 clinical trial of single agent RP1 in solid organ transplant recipients with skin cancers, including CSCC, which is referred to herein as ARTACUS or the ARTACUS trial, which we believe to be potentially registrational (in its own right or, subject to discussion with regulatory authorities, following enrollment of additional patients, including as a potential label expansion after an initial approval of RP1 in a different indication).

We are currently enrolling up to 65 patients in the ARTACUS trial to assess the safety and efficacy of RP1 in liver, kidney, heart, lung, and hematopoietic cell transplant patients transplant recipients with skin cancers.

Enrollment in this clinical trial had been impacted by COVID-19, as the patient population is severely immune-compromised and considered very high risk, however, more recently we have seen enrollment increase in the ARTACUS trial.

As reported in March 2022, we have observed responses in these patients with RP1 as monotherapy with a similar safety profile to that observed in our other RP1 clinical trials in patients who are not immune suppressed.

Enrollment continues in the ARTACUS trial and we expect to present updated initial data at the American Transplant Congress in June 2023.

In addition to these ongoing trials with RP1, we are currently evaluating all strategic opportunities for RP1 in skin cancers, including the setting for the confirmatory clinical trial in melanoma which is expected to be required to support a potential accelerated approval of RP1 in anti-PD1 failed melanoma.

We are also developing additional product candidates, RP2 and RP3, that have been further engineered to enhance anti-tumor immune responses and are intended to address additional tumor types, including traditionally less immune responsive tumor types.

In December 2023, we reported the full data set of 156 patients (140 patients from the registration-directed expansion cohort and 16 anti-PD1 failed cutaneous melanoma patients from the prior phase 2 cohort), by investigator assessment, with an overall response rate, or ORR, of 31.4% and a complete response rate, or CR, of 12%.

RP1 combined with nivolumab continues to be well-tolerated, with mainly Grade 1-2 “on target” side effects, observed.

Following a Type C meeting with the U.S.

Food and Drug Administration, or FDA, a Phase 3 study design was agreed.

This confirmatory study, our IGNYTE-3 trial, is a randomized, controlled, multicenter, open-label Phase 3 clinical study comparing RP1 in combination with nivolumab versus physician's choice treatment for patients with unresectable Stage IIIb-IV cutaneous melanoma whose disease progressed on an anti PD-1 and an anti-CTLA-4 containing regimen (administered either as a combination regimen or in sequence) or who are not candidates for treatment with an anti-CTLA-4 therapy.

The FDA requested that the IGNYTE-3 trial be underway at the time of a BLA submission under the accelerated approval pathway and we plan to enroll patients into this trial in the second half of 2024.

The FDA also indicated that all responding patients in the IGNYTE anti-PD-1 failed cohort of melanoma patients should be followed for at least 6 months with assessments completed through independent central review using RECIST v1.1, in addition to modified RECIST used in the study.

Topline primary data from RP1 in combination with nivolumab in anti-PD-1 failed melanoma patients is expected in the second quarter of 2024 and we plan to submit a BLA for this cohort in the second half of 2024.

In our non-melanoma skin cancer, or NMSC, cohort of the IGNYTE clinical trial, we provided a data update in December 2023 from the first 30 patients with at least 6 months of follow up including patients with cutaneous squamous cell carcinoma, or CSCC, Merkel cell carcinoma, or MCC, basal cell carcinoma, and angiosarcoma in this cohort.

The data showed that treatment with RP1 in combination with nivolumab led to an ORR of 30% which is consistent with data from the anti-PD-1 failed melanoma cohort with approximately one-third of patients responding and 60% demonstrating clinical benefit.

combination of RP1 and nivolumab was well tolerated in this patient population with a safety profile consistent with the overall experience seen with this treatment regimen to date.

Enrollment remains open in this cohort.

Furthering development of our RP1 clinical candidate, we have open for enrollment a Phase 1b/2 clinical trial of single agent RP1 in solid organ transplant recipients with skin cancers, including CSCC, which is referred to herein as ARTACUS or the ARTACUS trial, which we believe to be potentially registrational (subject to discussion with regulatory authorities).

We are currently enrolling up to 65 patients in the ARTACUS trial to assess the safety and efficacy of RP1 in liver, kidney, heart, lung, and hematopoietic cell transplant patients with skin cancers.

In November 2023 we presented initial data from the ARTACUS clinical trial of RP1 monotherapy in solid organ transplant recipients with skin cancers at the Society for Immunotherapy of Cancer’s, or SITC, 38th Annual Meeting.

The data included 23 evaluable patients with CSCC (n=20) and MCC (n=3), demonstrating an ORR of 34.8% with responses observed in 6 CSCC patients and 2 patients with MCC.

Additional biomarker data collected showed an increase in CD+8 T, a type of immune cell, and an increase in the expression of PD-L1, after treatment suggesting immune activation.

RP1 monotherapy was well tolerated in these patients and the safety profile was similar to that observed in our other RP1 clinical trials in patients who are not immune suppressed.

No immune-mediated adverse events or evidence of allograft rejection were observed.

This data was also presented during oral presentation at the American Association of Cancer Research, or AACR, 2024 Annual Meeting in April 2024.

We continue to enroll patients into this trial.

As reported in December, our randomized, controlled Phase-2 clinical trial of RP1 with CSCC, referred to as CERPASS or the CERPASS trial, under agreement with our partner Regeneron did not meet either of the two primary endpoints.

RP1 in combination with cemiplimab increased the CRR versus cemiplimab alone (38.1% vs.

25%, p=0.040), which was just short of the required threshold for statistical significance in this study.

The ORR was comparable between the two study groups (52.5% for RP1 plus cemiplimab vs.

51.4% for cemiplimab alone, p=0.692).

Notably, among the 83 patients with locally advanced disease, the complete response rate in the RP1 plus cemiplimab group was 48.1% versus 22.6% in the cemiplimab only group.

RP1 in combination with cemiplimab increased duration of response, or DOR, as compared to cemiplimab alone.

The CERPASS trial will continue as planned to assess DOR, progression free survival, or PFS, and overall survival, or OS, with greater maturity.

We are also developing or have been developing additional product candidates, RP2 and RP3, that have been further engineered to enhance anti-tumor immune responses and are intended to address additional tumor types, including traditionally less immune responsive tumor types.

In addition to the expression of GALV-GP R(-) and human GM-CSF as in RP1, RP2 has been engineered to express an antibody-like molecule intended to block the activity of CTLA-4, a protein that inhibits the full activation of an immune response, including to tumors.

RP3 has been engineered with the intent to further stimulate an anti-tumor immune response through activation of immune co-stimulatory pathways through the additional expression of the ligands for CD40 and 4-1BBL, as well as anti-CTLA-4 and GALV-GP R(-), but without the expression of GM-CSF.

We initiated a Phase-1 clinical trial of RP2 alone and in combination with nivolumab in the second half of 2019.

This clinical trial is also being conducted as part of our collaboration with BMS, under which BMS has granted us a non-exclusive, royalty-free license to, and will supply at no cost, nivolumab, for use in combination with RP2.

We have presented data from the single agent RP2 portion of this clinical trial that showed deep and durable responses, including demonstration of tumor response in uninjected lesions and in patients with difficult to treat advanced cancers.

We believe that this data supports the hypothesis that anti-CTLA-4 delivered intra-tumorally through oncolytic virus replication, with accompanying antigen release and presentation, can provide potent anti-tumor effects.

We have also presented combination data from both the clinical trial

that showed compelling activity in patients with immune insensitive tumors and with anti-PD-1 failed disease.

In the second half of 2021, we reported full enrollment in the initial 30 patient combination with nivolumab part of the Phase 1 clinical trial following which a protocol amendment was made to expand this clinical trial to enroll additional patients who are required to have specific tumor types of interest, including gastro-intestinal cancers, breast cancer, lung cancer, head and neck cancer and uveal melanoma, rather than any type of tumor as were eligible for the initial 30 patient group.

In December 2022, we reported that of 14 patients with uveal melanoma for which sufficient follow-up was available for assessment, 4 patients had achieved a response.

Enrollment continues in our clinical trial designed to evaluate RP3 alone and combined with anti-PD-1 therapy in advanced solid tumor patients, focusing on enrolling patients with gastro-intestinal cancers, breast cancer, lung cancer and head and neck cancer.

In December 2022, the Company presented data from its Phase 1 trial of RP3 in combination with nivolumab (N=5) in patients with multiple soft tissue sarcomas including in leiomyosarcoma, osteosarcoma, chondrosarcoma, and epithelioid sarcomas who have all failed standard of care.

At the data cut-off date, 3 of 5 patients had sufficient follow-up for response assessment, and all three were responding to therapy in settings with no viable alternative treatment option, indicating the potential utility of RP3 in treating this difficult to treat tumor type.

Accrual in the Phase 1 programs with both RP2 and RP3 are expected to materially complete in Q3 2023.

Any additional Phase 2 development programs not already announced which are driven by data from the full Phase 1 data and other opportunistic considerations are expected to be disclosed by year-end 2023.

We continue to plan for our previously announced Phase 2 development program for RP2 and/or RP3 that we expect to initiate around mid-year 2023.

We are planning for initial signal finding single arm Phase 2 clinical trials in the following tumor types:

squamous cell carcinoma of the head and neck, or SCCHN, locally advanced and recurrent/metastatic;

hepatocellular carcinoma, or HCC, both first and second line;

and colorectal cancer, or CRC, third line;

with additional studies in other tumor types intended to follow.

As we announced in December 2022, our signal finding studies in HCC and CRC are being developed in combination with atezolizumab and bevacizumab under a supply and cost share clinical collaboration arrangement with Roche Holding AG, or Roche.

Our signal finding studies in SCCHN are being developed in combination with nivolumab under our collaboration agreement with BMS.

– In HCC, two signal finding cohorts of 30 patients each will be enrolled in collaboration with Roche.

The first cohort will enroll 1L patients treated with SOC atezolizumab combined with bevacizumab and RP3, and the second cohort will enroll patients who have progressed on 1L immunotherapy (including atezolizumab/bevacizumab), and will be treated with atezolizumab combined with bevacizumab and RP3.

– In CRC, two signal finding cohorts of 30 patients each will be enrolled in collaboration with Roche.

The first cohort will enroll 3L patients to be treated with atezolizumab combined with bevacizumab and RP2 and the second cohort with atezolizumab and bevacizumab and RP3.

We believe that data with both RP2 and RP3 in CRC will allow the comparative efficacy of RP2 and RP3 to be evaluated in a particularly difficult to treat patient population.

– In SCCHN, the trial will be conducted under our collaboration with BMS.

This study is intended to include two cohorts of patients, the first with locally advanced disease is planned to enroll approximately 100 patients randomized 1:1 to either SOC chemotherapy combined with radiation, or SOC combined with RP3 followed by adjuvant nivolumab therapy.

The second, signal finding cohort, will enroll 30 patients with recurrent or metastatic SCCHN with low PD-L1 levels (CPS<20) who will be treated with chemotherapy, nivolumab and RP3.

RP1, RP2 and RP3 are administered by direct injection into solid tumors, guided either visually or by ultrasound, computerized tomography, or CT, or other imaging methods.

We continue the development of our clinical candidate RP2 with a focus on establishing a rare cancer franchise.

Notably, as previously reported, from our Phase-1 clinical trial of RP2 alone and in combination with nivolumab, we have seen durable responses from a monotherapy cohort in a variety of difficult to treat tumors as well as in combination with anti-PD1 and in particular in patients with uveal melanoma, among other tumor types.

In November 2023, we presented updated data from a cohort of metastatic uveal melanoma patients during a Plenary Session at the 20th Annual International Society for Melanoma Research Congress.

The updated data showed RP2 led to an ORR of 29.4 percent (5 of 17 patients;

one of the responding patients was treated with RP2 monotherapy and four of the responding patients were treated with RP2 combined with nivolumab), including responses in patients with liver, lung, and bone metastases.

The median DOR at the data cutoff was 11.47 months (range of 2.78 to 21.22 with responses ongoing).

Nearly all patients (15 of 17, 88.2%) in the study had progressed on or after immunotherapy with 12 of 17 patients (70.6%) having previously received both anti-PD1 and anti-CTLA-4 therapies, including four of the responding patients.

RP2 was generally well tolerated both as monotherapy and in combination with nivolumab with no additive adverse events observed.

The most common grade 1 or 2 treatment related adverse events, or TRAEs, overall in both cohorts were pyrexia, chills, fatigue, hypotension and pruritis.

Six patients had grade 3 TRAEs, including two cases of hypotension and no patients had grade 4 or 5 TRAEs.

Based on the data in this population, we are near final in the development of a registrational clinical trial protocol with RP2 combined with nivolumab in advanced uveal melanoma following input from the FDA.

As previously announced, our development program in hepatocellular carcinoma, or HCC, that we are collaborating on with Roche for the supply of its currently approved drugs, atezolizumab and bevacizumab, has been limited to the 2L setting and will use RP2 rather than RP3.

The Phase 2 clinical trial with RP2 in anti-PD1/PD-L1 progressed HCC with RP2 combined with atezolizumab and bevacizumab is expected to initiate in the second half of 2024.

Although our RP2/3 development in squamous cell carcinoma of the head and neck and colorectal cancer, or CRC, have been discontinued, as previously announced, we are continuing to treat patients who were already in screening or enrolled in these trials before the trials were discontinued.

RP1, RP2 and RP3 are administered by direct injection into solid tumors, guided either visually or by ultrasound, computerized tomography or other imaging methods.

We believe that direct injection maximizes virus-mediated tumor cell death, provides the most efficient delivery of virus-encoded immune activating proteins into the tumor with the goal of activating systemic immunity, and limits the systemic toxicities that could be associated with intravenous administration.

1 unchanged sentence

Our approach — Oncolytic immunotherapy

Our product candidates are designed to induce a robust immune response against a patient’s cancer and turn immunologically “cold” tumors “hot.” To achieve this objective, we use oncolytic immunotherapies that combine multiple mechanisms of action in a single product candidate.

Our product candidates are designed to induce a robust immune response against a patient’s cancer.

To achieve this objective, we use oncolytic immunotherapies that combine multiple mechanisms in a single product candidate.

We believe our product candidates will initiate or enhance an immune response in patients with no or minimal pre-existing cancer immunity, including to tumor neo-antigens, and thereby increase the effectiveness of immune checkpoint blockade therapies.

Our product candidates are intended to act at several key points in the pathways involved in the initiation of an immune response.

Following direct injection into tumors, our viruses replicate in cancer cells and then lyse, or break them open, releasing tumor antigens, including neo-antigens specific to the patient, which could otherwise be hidden from the immune

This process of necrotic cell death releases intra-cellular markers of “danger,” the danger associated molecular patterns, or DAMPs, while the virus produces pathogen associated markers of danger, or PAMPs.

21 unchanged sentences

With the intention of further amplifying the anti-tumor response, we have also engineered product candidates that express a range of additional potent, immune activating genes encoding therapeutic proteins in tumors.

Our lead product candidate, RP1, serves as the base from which our additional product candidates, RP2 and RP3, are being developed to express additional therapeutic proteins.

We believe that our sequential development approach of further enhancing our product candidates with additional therapeutic proteins reduces clinical risk, as we are able to study the safety profile of each therapeutic protein prior to moving to the next product candidate with an additional therapeutic protein that is intended to provide more potent anti-tumor immune effects.

RP1 serves as our lead product candidate, with additional product candidates, RP2 and RP3, designed to express additional therapeutic proteins.

We believe that our development approach of further enhancing our product candidates with additional therapeutic proteins reduces clinical risk, as we are able to study the safety profile of each therapeutic protein that is intended to provide more potent anti-tumor immune effects.

Lead product candidate:

11 unchanged sentences

By expressing anti-CTLA-4 only locally in the tumor and draining lymph nodes, we believe that activity will be retained, but that toxicity will be reduced.

We intend that our RP2 product candidate will be used in combination with other treatment approaches, including anti-PD-1 therapy, which we believe will result in both synergy with the oncolytic immunotherapy and the expression of anti-CTLA-4 in the tumor.

We expect that our RP2 product candidate will be used as monotherapy and/or in combination with other treatment approaches, including anti-PD-1 therapy, which, when used in combination, we believe will result in both synergy with the oncolytic immunotherapy and the expression of anti-CTLA-4 in the tumor.

We have designed our RP3 product candidate to express further immune-activating proteins that stimulate T cells, in addition to anti-CTLA-4 and GALV-GP R(-).

These immune activating proteins are the ligands for two immune co-stimulatory pathways responsible for T cell proliferation and/or activation, the CD40L and 4-1BBL pathways.

As previously announced, we have discontinued development of RP3 at this time.

Intellectual property

We believe our rights under issued patents, if obtained, and patent applications will provide a competitive advantage.

We believe our rights under our issued patents and, anticipated future patents from our patent applications, will provide a competitive advantage.

Our success depends in part on our ability to obtain and maintain proprietary protection for our product candidates, technology and know-how, to operate without infringing the proprietary rights of others and to prevent others from infringing upon our proprietary rights.

1 unchanged sentence

We also rely on trade secrets, know-how and continuing technological innovation to develop and maintain our proprietary position.

For the core technology in our RPx platform and each of our product candidates, we have filed six patent applications under the Patent Cooperation Treaty, or PCT.

For the core technology in our RPx platform and each of our product candidates, we initially filed six patent applications under the Patent Cooperation Treaty, or PCT.

All six of these PCT applications have entered the national phase and are in different stages of pending and/or issued in a range of countries.

Examination has started in connection with some of the national phase applications.

Six US patents have been granted by the applicable authorities in the US.

Four European patents have been granted by the applicable authorities in the European Union, two patents have been granted by the applicable authorities in Hong Kong and three patents have been granted by the applicable authorities in Japan, two patents have been granted by the applicable authorities in Israel, and one patent has been granted by the applicable authorities in each of Singapore, China and Australia.

The granted US patents include US patent numbers 10,570,377;

Patent examination has started and continues in these national phase applications.

patents have been granted by the applicable authorities in the U.S.

Four patents have been granted by the applicable authorities in each of the European Union and Japan.

Three patents have been granted by the applicable authorities in Hong Kong, two patents have been granted by the applicable authorities in each of China and Israel and one patent has been granted by the applicable authorities in each of Singapore, India, Mexico and Australia.

The granted U.S.

patents include US patent numbers 10,570,377;

and 11,473,063 and include description and claims directed to oncolytic virus compositions of matter, pharmaceutical compositions encompassing an oncolytic virus and methods of use in treating cancer with oncolytic virus compositions.

Two of our European patents have been opposed, one of which was recently successfully maintained and the other remains under the opposition process.

One of our US patents has been petitioned for post-grant review and one of our Japanese patents has been maintained as granted following being opposed.

We have successfully defended all oppositions that have been brought by third-parties against our issued patents to-date and have maintained our proprietary position.

We continue to vigorously pursue advancement and defense of our patents and patent applications through the respective patent offices in which they are granted or pending throughout the world.

1 unchanged sentence

The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.

In most countries in which we file, the patent term is 20 years from the earliest date of filing a non-provisional patent application.

In many countries in which we file, the patent term is 20 years from the earliest date of filing a non-provisional patent application.

In the United States, the patent term of a patent that covers an FDA-approved drug may also be eligible for patent term extension, which permits patent term restoration of a portion of the patent term lost during the U.S.

4 unchanged sentences

Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a patent that covers an approved drug.

In the future, if and when our products receive FDA approval, and if and when patents grant, we expect to apply for patent term extensions on patents covering those products.

We plan to seek

patent term extensions to any of our issued patents in any jurisdiction where these are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions.

In the future, if and when our products receive FDA approval, and if

and when patents grant, we expect to apply for patent term extensions on patents covering those products.

We plan to seek patent term extensions to any of our issued patents in any jurisdiction where these are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions.

We may rely, in some circumstances, on trade secrets to protect our technology.

12 unchanged sentences

• cancer vaccines including personalized vaccines and those targeting tumor neo-antigens;

• cell-based therapies, such as CAR-T, T cell receptor-based, and NK cell therapies.

• cell-based therapies, such as CAR-T, T cell receptor-based, and natural killer, or NK, cell therapies.

Our commercial opportunity will be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer side effects, are easier to administer or are less expensive alone or in combination with other therapies than any products that we may develop alone or in combination with other therapies, especially if these get to market sooner than our products.

3 unchanged sentences

At the same time, however, we believe that our oncolytic product candidates, if and when ultimately marketed, would likely be used principally in combination with checkpoint blockade therapies in addition to existing cancer therapies, including surgery, chemotherapy, radiation therapy and other biological therapies such as antibodies targeting particular surface receptors.

We therefore believe that our product candidates, if and when marketed, would largely complement rather than compete directly with these existing treatment options.

We therefore believe that our product candidates, if and when marketed, would largely complement rather than compete directly with some of these existing treatment options.

We do, however, expect to face direct and increasing competition from a number of companies that are also seeking to develop cancer therapies based on oncolytic viruses and other ways to prime the immune system, including neo-antigen vaccination.

12 unchanged sentences

We are also developing our product candidates for maximum practicality of use compared with some other oncolytic immunotherapies.

Traditionally, our third-party contract manufacturer in Europe has been responsible for the cGMP manufacture and filling of our product candidates for use in our clinical trials.

We have established our raw material supply chain for our product candidates as part of the process of establishing and qualifying our own manufacturing facility and intend to enter into commercial supply, collaboration or similar agreements as needed to operate the in-house manufacturing of our product candidates for our clinical trials and, if approved, build commercial supply of our products.

Traditionally, our third-party contract manufacturer in Europe had been responsible for the cGMP manufacture and filling of our product candidates for use in our clinical trials.

We have established our raw material supply chain for our product candidates as part of the process of establishing and qualifying our own manufacturing facility and intend to enter into commercial supply, collaboration or similar agreements as needed to continue to operate the in-house manufacturing of our product candidates for our clinical trials and, if approved, build commercial supply of our products.

Our approximately 63,000 square foot manufacturing facility in Framingham, Massachusetts is fully operational.

5 unchanged sentences

The facility is intended to give us control over key aspects of the supply chain for our products and product candidates.

We recently completed a successful Type C meeting with the FDA that confirmed alignment on our chemistry, manufacturing, and controls, or CMC, plans to support our BLA submission for RP1 in the second half of 2024.

By establishing our own manufacturing facility, we aim to minimize or eliminate our reliance on contract manufacturing organizations, which typically have limited capacity at commercial scale and long-lead time to conduct manufacturing campaigns.

4 unchanged sentences

If and when our product candidates receive marketing approval, we intend to commercialize them on our own in the United States and potentially with pharmaceutical or biotechnology partners in other geographies.

In January 2023, we announced the strengthening of our executive team with the appointment of Christopher Sarchi as our Chief Commercial Officer and the appointment of Sushil Patel, Ph.D., previously Replimune’s Chief Commercial Officer, to a newly created position of Chief Strategy Officer.

Following these appointments, we have further built our in-house sales, marketing or commercialization capabilities with the addition of sales, marketing, trade and distribution, as well as other related expertise.

Clinical data, the size of the opportunity for our product candidates, RP1, RP2 and RP3, and the size of the commercial infrastructure required will influence our commercialization plans and decision making.

We continue to build our in-house sales, marketing and commercialization capabilities with the addition of sales, marketing, trade and distribution, as well as other related expertise.

Clinical data, the size of the opportunity for our product candidates, and the size of the commercial infrastructure required will influence our commercialization plans and decision making.

Collaborations

3 unchanged sentences

BMS granted us a non-exclusive, non-transferrable, royalty-free license (with a right to sublicense) under its intellectual property to use nivolumab in the clinical trial and has agreed to supply nivolumab, at no cost to us, for use in the clinical trial.

Both parties will own the study data produced in the clinical trial, other than study data related solely to

nivolumab, which will belong solely to BMS, or study data related solely to RP1, which will belong solely to us.

Both parties will own the study data produced in the clinical trial, other than study data related solely to nivolumab, which will belong solely to BMS, or study data related solely to RP1, which will belong solely to us.

In January 2020, this agreement was expanded to cover an additional cohort of 125 patients with anti-PD-1 failed melanoma.

6 unchanged sentences

Pursuant to the agreement we agreed to undertake one or more clinical trials with Regeneron for the administration of our product candidates in combination with cemiplimab, an anti-PD-1 therapy developed by Regeneron, across multiple solid tumor types.

The first of which, agreed in June 2018, is our ongoing Phase 2 clinical trial testing RP1 in combination with cemiplimab versus cemiplimab alone in patients with CSCC.

The first of which, agreed in June 2018, is our ongoing clinical trial testing RP1 in combination with cemiplimab versus cemiplimab alone in patients with CSCC.

Each clinical trial will be conducted pursuant to an agreed study plan which, among other things, will identify the name of the sponsor and which party will manage the particular study, and include the protocol, the budget and a schedule of clinical obligations.

The first study plan related to the Phase 2 clinical trial in CSCC has been agreed.

Pursuant to the terms of the agreement, each party granted the other party a non-exclusive license of their respective intellectual property and agreed to contribute the necessary resources needed to fulfill their respective obligations, in each case, under the terms of agreed study plans.

Development costs of a particular clinical trial will be split equally.

In July 2022, Regeneron informed the Company that the costs of the study have reached the initial budget for the initial study plan of June 2018 and that Regeneron's reimbursement of CERPASS study costs to the Company have completed in the period ending June 30, 2022 in relation to the initial study budget.

As a result of this notice from, and the ongoing communications with, Regeneron, we have not recorded any cost-sharing reimbursements from Regeneron in prepaid expenses and other current assets in the consolidated balance sheet or as an offset to research and development expense within the consolidated statement of operations since Regeneron informed us that Regeneron’s reimbursement of CERPASS study costs have completed.

The Company does not expect any further reimbursements from Regeneron related to the initial study plan of June 2018.

The Company does not expect any further reimbursements from Regeneron related to the initial study plan of June 2018 and the CERPASS trial.

The agreement contains representations, warranties, undertakings and indemnities customary for a transaction of this nature.

2 unchanged sentences

The agreement may be terminated by either party if (i) there is no active study plan for which a final study report has not been completed and the parties have not entered into a study plan for an additional clinical trial within a period of time after the delivery of the most recent final study report or (ii) in the event of a material breach.

In December 2022, we announced entering into a Master Clinical Trial Collaboration and Supply Agreement with Roche in relation to our RP2 and RP3 programs in colorectal cancer, or CRC, and hepatocellular carcinoma, or HCC.

Under the agreement, the companies will collaborate in 30 patient cohort signal finding studies in third-line, or 3L, CRC and in first- and second-line, or 1L and 2L, respectively, HCC.

Under the terms of the agreement, the companies will share costs and Roche will supply its currently approved drugs, atezolizumab and bevacizumab for 2L HCC and 3L CRC combined with RP3.

Roche will also supply atezolizumab and bevacizumab for 1L HCC combined with RP3, and for 3L CRC combined with RP2.

We have retained the responsibility of operating the clinical trials as well as retaining all the rights to the development and commercialization of our product candidates.

In December 2022, we entered into a Master Clinical Trial Collaboration and Supply Agreement with Roche in relation to our RP2 and RP3 programs in colorectal cancer, or CRC, and hepatocellular carcinoma, or HCC.

Under the agreement, the companies intended to collaborate in 30 patient cohort signal finding studies in third-line, or 3L, CRC and in first- and second-line, or 1L and 2L, respectively, HCC.

Following our re-prioritization of our product development portfolio in December 2023, we have agreed with Roche to terminate the CRC collaboration and pursue the 2L cohort in HCC with RP2 only.

Roche has expressed its intent to continue to supply its currently approved drugs, atezolizumab and bevacizumab for the 2L cohort in HCC but is unlikely to share costs following our re-prioritization.

We are in discussions with Roche about revising these agreements following our changes to our RP2 and RP3 development plans.

Under the terms of the initial agreement we retained the responsibility of operating the clinical trials as well as retaining all the rights to the development and commercialization of our product candidates.

The agreement may be terminated by either party upon sixty days prior written notice to the other party.

In July 2023, we entered into a Clinical Trial Collaboration and Supply Agreement with Incyte Corporation, or Incyte.

Under the agreement, the companies anticipate collaborating in a signal finding study in which Incyte will initiate and sponsor a clinical trial of INCB99280 (oral PD-L1 inhibitor) and RP1 in approximately 40 patients with unresectable, high risk CSCC in the neoadjuvant setting.

Under the terms of the agreement, we will supply Incyte with RP1 for the study and share costs of the study equally with Incyte.

The agreement may be terminated by either party upon (i) a material breach not reasonably cured within thirty days;

(ii) the discontinuation of development of its clinical drug candidate;

(iii) the unethical or illegal business practices of the other party;

or (iv) if the parties have not agreed on the protocol or budget within ninety days of the effective date of the agreement.

In addition, the Company may terminate the agreement upon the inappropriate or unsafe use of the RP1

product candidate.

As of March 31, 2024, we and Incyte had not yet agreed on the protocol or budget.

However, we and Incyte continue to discuss a potential protocol and neither party has triggered termination of the agreement in accordance with the termination right described in clause (iv) above.

The parties are evaluating potential collaboration efforts pending further CERPASS data readout of RP1 in combination with cemiplimab and additional data for Incyte's product candidate INCB99280.

Regulatory matters

4 unchanged sentences

By example, the FDA and governmental authorities in other countries have issued a growing body of guidance documents on various regulatory matters, including those specific to cell and gene therapy development.

While FDA’s guidance is not binding, it does provide FDA’s current interpretation and approach.

FDA and EU regulation

50 unchanged sentences

In general, for purposes of BLA approval, human clinical trials are typically conducted in three sequential phases, which may overlap, be divided, or be combined.

• Phase 1 — Trials are initially conducted in healthy human volunteers or subjects with the target disease or condition and test the product candidate for safety, dosage tolerance, structure-activity relationships, mechanism of action, absorption, metabolism, distribution, and excretion.

absorption, metabolism, distribution, and excretion.

If possible, Phase 1 trials may also be used to gain an initial indication of the activity of the product candidate.

14 unchanged sentences

While certain criteria must be met for a patient to be eligible for access to product candidates under right to try laws, these laws do not require the FDA to approve the use of the product candidate and do not require compliance with the majority of the FDA’s clinical trial regulations.

The FDA may also require, or companies may conduct, additional clinical trials for the same indication after a product is approved.

The FDA may also require, or companies may conduct, additional clinical trials for the same indication after a product is approved to further assess the product’s safety and effectiveness, and to ensure that population representative data is collected.

These so-called Phase 4 trials may be made a condition to be satisfied after approval.

6 unchanged sentences

However, enforcement of such rules is conducted by the regulatory authority in which the trial is carried out, which is the MHRA in the United Kingdom.

With the full departure of the United Kingdom from the European Union in January 2021, the United Kingdom is not covered by the European Union Clinical Trial Regulation, in force since January 2022, which inter alia introduced a portal to streamline cross-border trial applications, and is instead subject to rules equivalent to the previous 2001 EU Clinical Trials Regulation.

With the full departure of the United Kingdom from the European Union in January 2021, the United Kingdom is not covered by the European Union

Clinical Trial Regulation, in force since January 2022, which inter alia introduced a portal to streamline cross-border trial applications, and is instead subject to rules equivalent to the previous 2001 EU Clinical Trials Regulation.

Combination Products

Biologic products may be regulated as combination products if they are intended for use in conjunction with medical devices, such as a delivery device.

In such cases, the use of the two products together (i.e., the biological product and the

device) must be shown to be safe and effective for the proposed intended use, and, the labeling of the two products must reflect their combined use.

In such cases, the use of the two products together (i.e., the biological product and the device) must be shown to be safe and effective for the proposed intended use, and, the labeling of the two products must reflect their combined use.

In some cases, the device component may require a separate premarket submission;

22 unchanged sentences

Under the goals and policies agreed to by the FDA under the Prescription Drug User Fee Act, or PDUFA, the FDA has set the review goal of completing its review of 90% of all applications within ten months from the 60-day filing date for its initial review of a BLA.

This review goal is referred to as the PDUFA date.

The PDUFA date is only a goal, thus, the FDA does not always meet its PDUFA dates.

The review process and the PDUFA date may also be extended if the FDA requests or the sponsor otherwise provides substantial additional information or clarification regarding the submission.

The FDA does not always meet its PDUFA goal dates for BLA submissions, and the review process may be extended if the FDA requests or the sponsor otherwise provides additional information or clarification regarding the submission.

The FDA may also refer certain applications to an advisory committee.

An advisory committee is typically a panel that includes clinicians and other experts, which review, evaluate, and make a recommendation as to whether the application should be approved and under what conditions.

An advisory committee is typically a panel that includes clinicians and other experts, and may at times includes patients, which review, evaluate, and make a recommendation

as to whether the application should be approved and under what conditions.

The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

1 unchanged sentence

Before approving a BLA, the FDA typically will inspect or conduct a remote regulatory assessment of the facility or facilities where the product is manufactured, referred to as a Pre-Approval Inspection.

The FDA will not approve an application unless it determines that the manufacturing processes and facilities, including contract manufacturers and subcontractors, are in

compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

The FDA will not approve an application unless it determines that the manufacturing processes and facilities, including contract manufacturers and subcontractors, are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

Additionally, before approving a BLA the FDA will inspect or conduct a remote regulatory assessment of one or more clinical trial sites to assure compliance with GCPs.

17 unchanged sentences

While there is no direct equivalent to the separate route for biologics, broadly equivalent requirements and controls similarly apply to the submission of pediatric testing and marketing authorization applications to the European Medicines Agency in the European Union and, post-approval, to the holding of such marketing authorizations, including conditionality.

Additional FDA Expedited Review and Approval Programs

FDA’s fast track, priority review, accelerated approval, and breakthrough therapy programs are special programs and pathways at the agency that are intended to facilitate and expedite product development and approval.

Product candidates may be eligible for fast track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address an unmet medical need.

If a sponsor applies for and receives fast track designation, the designated product candidate may be eligible for more frequent FDA interactions as well as rolling review of sections of an application before the application is complete.

To qualify for rolling review, the applicant must provide and FDA must approve a schedule for the submission of the full application.

User fees must also be paid before FDA will commence its review of an application submitted on a rolling basis.

Priority review may be available to product candidates that are intended to treat serious conditions and, if approved, would provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of the serious condition.

If a product receives priority review, FDA’s PDUFA review goal is shortened to six months following FDA acceptance of a BLA, rather than the standard review of ten months.

Product candidates eligible for FDA’s accelerated approval pathway are those that are intended to treat serious or life-threatening illnesses that provide meaningful therapeutic benefit to patients over existing treatments.

Under this pathway, FDA may approve a marketing application based upon adequate and well-controlled clinical trials that evaluate a product candidate’s effect on a surrogate endpoint, which is an endpoint that is reasonably likely to predict clinical benefit, or a product’s effect on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality and that is reasonably likely to predict an effect on irreversible morbidity or mortality, taking into account the severity, rarity, or prevalence of the condition and availability or lack of alternative treatments.

Products approved under the accelerated approval pathway must complete Phase 4 clinical trials to demonstrate the product’s clinical benefit.

By the date of approval of an accelerated approval product, FDA must specify the conditions for the required post approval studies, including enrollment targets, the study protocol, milestones, and target completion dates.

FDA may also, and frequently does, require that the confirmatory Phase 4 studies be commenced prior to FDA granting a product accelerated approval.

If a Phase 4 study is not sufficiently advanced at the time of a marketing application, FDA can issue a complete response letter rather than approve the product.

Reports on the progress of the required Phase 4 confirmatory studies must be submitted to FDA every 180 days after approval.

If the confirmatory Phase 4 studies fail to verify the clinical benefit of the product, the FDA may withdraw approval of the application through a statutorily defined streamlined process.

Failure to conduct the required Phase 4 confirmatory studies or to conduct such studies with due diligence, as well as failure to submit the required update reports can subject a sponsor to penalties.

Promotional materials for a drug or biologic approved under the accelerated approval pathway are subject to FDA prior review.

A third program that may be available is the breakthrough therapy program, which is for products that are intended, alone or in combination with one or more other products, to treat a serious or life-threatening disease or condition, and for which preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

Breakthrough therapy products may be eligible for intensive FDA guidance on development programs as early as phase 1 clinical trials, FDA organization commitment to involve senior managers and experienced review and regulatory management staff in a proactive collaborative, proactive, and cross-disciplinary reviews, and marketing application rolling review.

FDA designations may be rescinded if the applicable qualifying criteria are no longer met.

Biosimilars and exclusivity

9 unchanged sentences

The biosimilar product sponsor and reference product sponsor may exchange certain patent and product information for the purpose of determining whether there should be a legal patent challenge.

outcome of negotiations surrounding the exchanged information, the reference product sponsor may bring a patent infringement suit and injunction proceedings against the biosimilar product sponsor.

Based on the outcome of negotiations surrounding the exchanged information, the reference product sponsor may bring a patent infringement suit and injunction proceedings against the biosimilar product sponsor.

The biosimilar applicant may also be able to bring an action for declaratory judgment concerning the patent.

5 unchanged sentences

If approved, biologics may also be eligible for periods of United States patent term restoration.

If granted, patent term restoration extends the patent life of a single unexpired patent, that has not previously been extended, for a maximum of five years.

If a timely application is made and if granted, patent term restoration extends the patent life of a single unexpired patent, that has not previously been extended, for a maximum of five years.

The total patent life with the extension also cannot exceed fourteen years from the product’s approval date.

Subject to the prior limitations, the period of the extension is calculated by adding half of the time from the effective date of an IND to the initial submission of a marketing application, and all of the time between the submission of the marketing application and its approval.

Subject to the prior limitations, the period of the extension is calculated by adding half of the time from the effective date of an IND to the initial submission of a full marketing application, and all of the time between the submission of the full marketing application and its approval.

This period may also be reduced by any time that the applicant did not act with due diligence.

10 unchanged sentences

In addition, manufacturers and other entities involved in the manufacture and distribution of approved therapeutics are required to register their establishments with the FDA and certain state agencies, list their products, and are subject to periodic announced and unannounced inspections or remote regulatory assessment by the FDA and these state agencies for compliance with cGMP and other requirements, which impose certain procedural and documentation requirements upon sponsors and third-party manufacturers.

Recently, the information that must be submitted to FDA regarding manufactured products was expanded through the Coronavirus Aid, Relief, and Economic Security, or CARES, Act to include the volume of drugs produced during the prior year.

The information that must be submitted to FDA regarding manufactured products was expanded through the Coronavirus Aid, Relief, and Economic Security, or CARES, Act to include the volume of drugs produced during the prior year.

Manufacturers must continue to expend time, money, and effort in the areas of production and quality-control to maintain compliance with cGMPs.

2 unchanged sentences

Changes to the manufacturing process are strictly regulated and often require prior FDA approval or notification before being implemented.

FDA regulations also require investigation and correction of any deviations from cGMP and specifications and impose reporting and documentation requirements upon the sponsor and any third-party manufacturers that the sponsor

may decide to use.

Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance.

The FDA also strictly regulates marketing, labeling, advertising, and promotion of products that are placed on the market.

A company can make only those claims relating to safety and efficacy, purity, and potency that are approved by the FDA.

Physicians, in their independent professional medical judgment, may prescribe legally available products for unapproved indications that are not described in the product’s labeling and that differ from those tested and approved by the FDA.

A company can make only those claims relating to safety and efficacy, purity, and potency that are consistent with the FDA approved label.

All promotional and advertising statements must further be truthful and non-misleading, adequately substantiated, and must contain a fair balance between product benefit and risk information.

Recently, FDA has taken a few actions in the advertising and promotional spaces, including issuing a final rule and a guidance on risk and efficacy disclosures in direct to consumer advertising, and a guidance on communication of off-label scientific information about approved products.

Biopharmaceutical companies, however, are required to promote their products only for the approved indications and in accordance with the provisions of the approved label.

2 unchanged sentences

Among the requirements of this legislation, manufacturers are required to provide certain information regarding the products to individuals and entities to which product ownership is transferred, are required to label products with a product identifier, and are required to keep certain records regarding the product.

The transfer of information to subsequent product owners by manufacturers is also required to be done electronically and will be required to be exchanged via an interoperable system at the package level by November 2023.

The transfer of information to subsequent product owners by manufacturers will also be required to be done electronically and will be required to be exchanged via an interoperable system at the package level (while this requirement was to go into effect in November 2023, FDA has stated that it does not intend to take action to enforce requirements for the interoperable, electronic, package level product tracing until November 27, 2024).

Manufacturers must also verify that purchasers of the manufacturers’ products are appropriately licensed.

8 unchanged sentences

As part of the CARES Act implementation, the FDA issued guidance on the reporting of the volume of drugs produced, which reporting will require additional administrative efforts by drug manufacturers.

In recent years, both the U.S.

Congress and the President have taken actions to encourage the use of domestic pharmaceutical suppliers and, there are also currently legislative proposals to limit the use of equipment and services provided by certain Chinese “biotechnology companies of concern”.

Broadly equivalent requirements, controls and sanctions similarly apply to supply, QA, manufacture, labelling, advertising, pharmacovigilance and tracing of medicinal products as imposed by European Union laws and enforced by European Union national regulatory authorities.

Additional controls for biologics

Additional controls for biologics and oncology programs

To help reduce the increased risk of the introduction of adventitious agents, the PHSA emphasizes the importance of manufacturing controls for products whose attributes cannot be precisely defined.

1 unchanged sentence

After a BLA is approved, the product may also be subject to official lot release as a condition of approval.

As part of the manufacturing process, the manufacturer is required to perform certain tests on each lot of the product before it is released for

distribution.

As part of the manufacturing process, the manufacturer is required to perform certain tests on each lot of the product before it is released for distribution.

If the product is subject to official release by the FDA, the manufacturer submits samples of each lot of product to the FDA together with a release protocol showing the results of all of the manufacturer’s tests performed on the lot.

6 unchanged sentences

In the European Union, while there is no direct equivalent to the separate route for biologics, the EMA issues scientific guidelines on biological medicinal products and the standard Common Technical Document structure is modified for biologicals and plasma-derived products.

With respect to oncology product candidates, FDA has also established a number of different projects, intended to address different aspects of oncology development.

For instance, FDA’s Project Optimus is an initiative at FDA to reform dose optimization and selection.

Project FrontRunner is aimed at encouraging drug sponsors to potentially pursue the development of products for earlier clinical settings, rather than for the treatment of patients who have received a number of different prior therapies.

Project Confirm is a third FDA initiative, which aims to promote transparency regarding the outcomes related to accelerated approval products.

Fraud and abuse, data privacy and security, and transparency laws and regulations

3 unchanged sentences

The term “remuneration” has been interpreted broadly to include anything of value.

The Anti-Kickback Statute has been interpreted to apply to arrangements between biopharmaceutical manufacturers on one hand and prescribers, purchasers, formulary managers, and beneficiaries on the other, as well as to free trial and starter prescriptions provided through pharmacies.

The Anti-Kickback Statute has been interpreted to apply to arrangements between biopharmaceutical manufacturers on one hand and prescribers, purchasers, and formulary managers, on the other, as well as to free trial and starter prescriptions provided through pharmacies.

There are certain statutory exceptions and regulatory safe harbors protecting some common activities from prosecution.

11 unchanged sentences

A claim includes “any request or demand” for money or property presented to the U.S.

The civil False Claims Act has been used to assert liability on the basis of kickbacks and other improper referrals, improperly reported government pricing metrics such as Best Price or Average Manufacturer Price, improper use of Medicare provider or supplier numbers when detailing a provider of

services, improper promotion of off-label uses not expressly approved by the FDA in a product’s label, and allegations as to misrepresentations with respect to products, contract requirements and services rendered.

The civil False Claims Act has been used to

assert liability on the basis of kickbacks and other improper referrals, improperly reported government pricing metrics such as Best Price or Average Manufacturer Price, improper use of Medicare provider or supplier numbers when detailing a provider of services, improper promotion of off-label uses not expressly approved by the FDA in a product’s label, and allegations as to misrepresentations with respect to products, contract requirements and services rendered.

In addition, private payers have filed follow-on lawsuits alleging fraudulent misrepresentation.

3 unchanged sentences

If the government declines to intervene, the individual may pursue the case alone.

The civil False Claims Act provides for treble damages and a civil penalty for each false claim, such as an invoice or pharmacy claim for reimbursement, which can aggregate into millions of dollars.

The civil False Claims Act provides for treble damages and a civil penalty for each false claim, such as an invoice or pharmacy claim for reimbursement, which can aggregate into hundreds of millions of dollars.

For these reasons, since 2004, civil False Claims Act lawsuits against biopharmaceutical companies have increased significantly in volume and breadth, leading to several substantial civil and criminal settlements, as much as $3.0 billion, regarding certain sales practices and promoting off label uses.

Civil False Claims Act liability may further be imposed for known Medicare or Medicaid overpayments that are not refunded within 60 days of discovering the overpayment, even if the overpayment was not caused by a false or fraudulent act.

In addition, conviction or civil judgment for violating the civil False Claims Act may result in exclusion from federal health care programs, suspension and debarment from government contracts, and refusal of orders under existing government contracts.

In addition, judgment for violating the civil False Claims Act may result in exclusion from participation in federal health care programs, suspension and debarment from government contracts, and refusal of orders under existing government contracts.

The government may further prosecute conduct constituting a false claim under the criminal False Claims Act.

3 unchanged sentences

Among other things, the civil monetary penalties statute imposes fines against any person who is determined to have knowingly presented, or caused to be presented, claims to a federal healthcare program that the person knows, or should know, is for an item or service that was not provided as claimed or is false or fraudulent.

Payment or reimbursement of prescription therapeutics by Medicaid or Medicare requires manufacturers to submit certified pricing information to CMS.

Payment or reimbursement of prescription therapeutics, including, but not limited to, by Medicaid or Medicare requires manufacturers to submit certified pricing information to CMS.

The Medicaid Drug Rebate statute requires manufacturers to calculate and report price points, which are used to determine Medicaid rebate payments shared between the states and the federal government and Medicaid payment rates for certain therapeutics.

The Medicaid Drug Rebate statute also imposes inflation penalties, and recent legislative proposals have called for removal of caps limiting the magnitude of these penalties and the implementation of new inflation penalties applicable to the Medicare program.

The Medicaid Drug Rebate statute also imposes inflation penalties, and recent legislative changes have removed the caps limiting the magnitude of these Medicaid penalties and the implementation of new inflation penalties applicable to the Medicare program.

In addition to the Medicaid statutory rebate, states are authorized to negotiate supplemental rebates on pharmaceuticals included in their formularies.

3 unchanged sentences

A Department of Defense regulation requires manufacturers to provide this discount on therapeutics dispensed by retail pharmacies when paid by the TRICARE Program.

All of these price reporting requirements create risk of submitting false information to the government, and potential FCA liability.

All of these price reporting requirements create risk of inadvertently submitting false information to the government, and potential FCA liability.

The VHCA also requires manufacturers of covered therapeutics participating in the Medicaid program to enter into Federal Supply Schedule contracts with the VA through which their covered therapeutics must be sold to certain federal agencies at FCP.

This necessitates compliance with applicable federal procurement laws and regulations, including submission of commercial sales and pricing information and certification of compliance with the Trade Agreements Act, and subjects us to contractual remedies as well as administrative, civil, and criminal sanctions.

This necessitates compliance with applicable federal procurement laws and regulations (e.g., Federal Acquisition Regulations), including submission of commercial sales and pricing information and certification of compliance with the Trade Agreements Act, and subjects us to contractual remedies as well as administrative, civil, and criminal sanctions.

In addition, the VHCA requires manufacturers participating in Medicaid to agree to provide different mandatory discounts to certain Public Health Service grantees and other safety net hospitals and clinics under the 340B program based on the manufacturer’s reported Medicaid pricing information.

The 340B program has its own regulatory authority to impose sanctions for non-compliance and adjudicate overcharge claims against manufacturers by the purchasing entities.

The federal Health Insurance Portability and Accountability Act of 1996, as amended, or HIPAA, also created federal criminal statutes that prohibit, among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any of the money or property owned by, or under the custody or control of, a healthcare benefit program, regardless of whether the payor is public or private, in connection with the delivery or payment for health care benefits, knowingly and willfully embezzling or stealing from a health care benefit program, willfully obstructing a criminal investigation of a health care offense and knowingly and willfully falsifying, concealing, or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items, or services relating to healthcare matters.

falsifying, concealing, or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items, or services relating to healthcare matters.

Additionally, the ACA amended the intent requirement of certain of these criminal statutes under HIPAA so that a person or entity no longer needs to have actual knowledge of the statute, or the specific intent to violate it, to have committed a violation.

6 unchanged sentences

The HITECH Act also strengthened the civil and criminal penalties that may be imposed against covered entities, business associates, and individuals, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions.

HIPAA imposes certain privacy requirements with respect to the use and disclosure of protected health information for research purposes, which will impact how we conduct our clinical trials.

In addition, other federal and state laws, such as the California Consumer Privacy Act, may govern the privacy and security of health and other information in certain circumstances, many of which differ from each other in significant ways and may not be preempted by HIPAA, thus complicating compliance efforts.

For example, certain states, such as Washington, Nevada and Connecticut, have enacted new privacy laws with respect to health data that is not protected health information governed by HIPAA.

Many states have also adopted laws similar to each of the above federal laws, which may be broader in scope and apply to items or services reimbursed by any third-party payor, including commercial insurers.

9 unchanged sentences

Coverage and reimbursement generally

The commercial success of our product candidates and our ability to commercialize any approved product candidates successfully will depend in part on the extent to which governmental payor programs at the federal and state levels, including Medicare and Medicaid, private health insurers, and other third-party payors, provide coverage for and establish adequate reimbursement levels for our product candidates.

Government authorities, private health insurers, and other organizations generally decide which therapeutics they will pay for and establish reimbursement levels for healthcare.

The commercial success of our product candidates and our ability to commercialize any approved product candidates successfully will depend in part on the extent to which governmental payor programs at the federal and state levels, including, but not limited to, Medicare and Medicaid, private health insurers, and other third-party payors, provide coverage for and establish adequate reimbursement levels for our product candidates.

Government authorities, private health insurers, and other

organizations generally decide which therapeutics they will pay for and establish reimbursement levels for healthcare.

Medicare is a federally funded program managed by CMS through local fiscal intermediaries and carriers that administer coverage and reimbursement for certain healthcare items and services furnished to the elderly and disabled.

Medicaid is an insurance program for certain categories of patients whose income and assets fall below state defined levels and who are otherwise uninsured that is both

federally and state funded and managed by each state.

Medicaid is an insurance program for certain categories of patients whose income and assets fall below state defined levels and who are otherwise uninsured that is both federally and state funded and managed by each state.

The federal government sets general guidelines for Medicaid and each state creates specific regulations that govern its individual program, including supplemental rebate programs that restrict coverage to therapeutics on the state Preferred Drug List.

1 unchanged sentence

Some states have also created pharmacy assistance programs for individuals who do not qualify for federal programs.

In the United States, private health insurers and other third-party payors often provide reimbursement for products and services based on the level at which the government provides reimbursement through the Medicare or Medicaid programs for such products and services.

In the United States, private health insurers and other third-party payors often provide reimbursement for products and services based on the level at which the government provides reimbursement through, amongst others, the Medicare or Medicaid programs for such products and services.

In the United States, the European Union, and other potentially significant markets for our product candidates, government authorities and third-party payors are increasingly attempting to limit or regulate the price of medical products and services, particularly for new and innovative products and therapies, which often has resulted in average selling prices lower than they would otherwise be and sometimes at or below the provider’s acquisition cost.

3 unchanged sentences

Third-party payors may limit coverage to specific therapeutic products on an approved list, or formulary, which might not include all of the FDA-approved products for a particular indication or might impose high copayment amounts to influence patient choice.

Third-party payors also control costs by requiring prior authorization or imposing other dispensing restrictions before covering certain products and by broadening therapeutic classes to increase competition.

Third-party payors also control costs by requiring prior authorization or imposing other dispensing restrictions, such as, but not limited to step edits, before covering certain products and by broadening therapeutic classes to increase competition.

Third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy.

5 unchanged sentences

Legislative proposals to reform healthcare or reduce costs under government programs may result in lower reimbursement for our product candidates or exclusion of our product candidates from coverage.

In addition, government programs like Medicaid include substantial penalties for increasing commercial prices over the rate of inflation.

In addition, government programs like Medicaid include substantial penalties for increasing commercial prices over the rate of inflation over the lifecycle of a product.

All of these conditions can affect realization and return on investment.

3 unchanged sentences

Further, the increased emphasis on managed healthcare in the United States and on country and regional pricing and reimbursement controls in the European Union will put additional pressure on product pricing, reimbursement, and utilization, which may adversely affect our future product sales and results of operations.

These pressures can arise from rules and practices of managed care groups, competition within therapeutic classes, judicial decisions and governmental laws and regulations related to Medicare, Medicaid, and healthcare reform, biopharmaceutical coverage and reimbursement policies, and pricing in general.

These pressures can arise from rules and practices of managed care groups, competition within therapeutic classes, judicial decisions and governmental laws and regulations related to, amongst others, Medicare, Medicaid, and healthcare reform, biopharmaceutical coverage and reimbursement policies, and pricing in general.

Patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs.

Sales of our product candidates will therefore depend substantially, both domestically and abroad, on the extent to which the costs of our products will be paid by health maintenance, managed care, pharmacy benefit and similar healthcare management organizations, or reimbursed by government health administration authorities, such as Medicare and Medicaid, private health insurers, and other third-party payors.

As a result of the above, we may need to conduct expensive pharmacoeconomic and/or health technology assessment studies in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain the FDA and EMA approvals.

Sales of our product candidates will therefore depend substantially, both domestically and abroad, on the extent to which the costs of our products will be paid by health maintenance, managed care, pharmacy benefit and similar healthcare management organizations, or reimbursed by government health administration authorities, such as, but not limited to, Medicare and Medicaid, private health insurers, and other third-party payors.

obtain the FDA and EMA approvals.

Our product candidates may not be considered medically necessary or cost-effective, or the rebate percentages required to secure coverage may not yield an adequate margin over cost.

Moreover, a payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved.

Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an

appropriate return on our investment in therapeutic development.

Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in therapeutic development.

Legislative or regulatory proposals to reform healthcare or reduce costs under government insurance programs may result in lower reimbursement for our products and product candidates or exclusion of our products and product candidates from coverage.

5 unchanged sentences

Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality, and expanding access.

In the United States, the biopharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.

In the United States, the biopharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives, such as, but not limited to, the Inflation Reduction Act and the Bayh-Dole Act march-in rights expansion.

For example, on November 27, 2020, CMS issued an interim final rule implementing a Most Favored Nation payment model under which reimbursement for certain Medicare Part B drugs and biologicals will be based on a price that reflects the lowest per capita Gross Domestic Product-adjusted (GDP-adjusted) price of any non-U.S.

3 unchanged sentences

This rule has now been rescinded, but similar programs have been described in recent legislative proposals.

Our results of operations could be adversely affected by current and future healthcare legislation and reforms.

Moreover, the ACA broadened access to health insurance, attempts to reduce or constrain the growth of healthcare spending, enhanced remedies against fraud and abuse, added new transparency requirements for healthcare and health insurance industries, imposed new taxes and fees on the health care industry, and imposed additional health policy reforms.

14 unchanged sentences

Some third-party payors also require pre-approval of coverage for new or innovative devices or therapies before they will reimburse healthcare providers that use such therapies.

While we cannot predict whether any proposed cost-containment

measures will be adopted or otherwise implemented in the future, the announcement or adoption of these proposals could have a material adverse effect on our ability to obtain adequate prices for our product candidates.

While we cannot predict whether any proposed cost-containment measures will be adopted or otherwise implemented in the future, the announcement or adoption of these proposals could have a material adverse effect on our ability to obtain adequate prices for our product candidates.

In addition, other legislative changes have been proposed and adopted since the ACA was enacted.

5 unchanged sentences

These and other healthcare reform initiatives may result in additional reductions in Medicare and other healthcare funding, which could have a material adverse effect on our financial operations.

We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could further limit the prices we are able to charge, or the amounts of reimbursement available, for our product candidates once they are approved.

The Bipartisan Budget Act also extended Manufacturer responsibility for prescription costs in the Medicare Part D coverage gap to biosimilars, which had previously been exempt.

2 unchanged sentences

individual or business from paying, offering, or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party, or candidate or representatives of international organizations for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business or obtaining an improper advantage.

The FCPA also obligates companies whose securities are listed in the United States to comply with books and records an accounting control provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.

The FCPA also obligates companies whose securities are listed in the United States to comply with books and records and accounting control provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.

Activities that violate the FCPA, even if they occur wholly outside the United States, can result in criminal and civil fines, imprisonment, disgorgement, oversight by compliance monitors, and suspension and debarment from government contracts, and refusal of orders under existing government contracts.

4 unchanged sentences

Set forth below is a description of certain of the target indications we currently intend to pursue with our product candidates.

Cutaneous squamous cell carcinoma

CSCC is the second most common form of skin cancer and is estimated to be responsible for at least 7,000 deaths each year in the United States.

It currently accounts for approximately 20% of all skin cancers in the U.S., with the number of newly diagnosed cases expected to rise annually.

When CSCC invades deeper layers of the skin or adjacent tissues, it is categorized as locally advanced.

Once it spreads to other distant parts of the body, it is considered metastatic.

Cemiplimab was the first approved therapy in the United States for the treatment of locally advanced or metastatic CSCC and has subsequently been approved in the European Union and Australia.

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin.

5 unchanged sentences

however, survival rates are roughly halved if regional lymph nodes are involved.

Solid Organ Transplant Skin Cancers

Individuals who receive an organ transplant face a significantly higher risk, greater than 50 times higher, of developing skin cancer following the transplant.

These individuals are also on chronic immuno-suppressive treatments to reduce the risk of transplant rejection by their immune system.

Adding to this risk for these individuals, anti-PD-1/L1 based cancer treatment options, which are approved and/or used in other skin cancer settings carry a high risk of transplant rejection, potentially leaving these patients without many treatment options.

In the United States, transplant rates have increased by roughly 50% over the last 8 years with an estimated 1,500 solid organ transplant patients with addressable skin cancer.

Non-melanoma skin cancers

Non-melanoma skin cancer, or NMSC, are a collection of common cancer types which occurs mainly in fair-skinned populations.

About 80% of all NMSC are basal cell carcinomas, squamous cell carcinomas represent about 20%, with other diagnoses representing around 1%.

Included in that 1% are primary cutaneous lymphoma, sarcomas of the skin, Merkel cell carcinoma, and appendageal carcinoma.

NMSC is often not routinely reported to cancer registries;

hence, accurate estimates of incidence are difficult to obtain.

The World Health Organization estimates 2 to 3 million cases per year.

Cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma is the second most common form of skin cancer and is estimated to be responsible for at least 7,000 deaths each year in the United States.

It accounts for approximately 20% of all skin cancers in the U.S., with the number of newly diagnosed cases expected to rise annually.

When CSCC invades deeper layers of the skin or adjacent tissues, it is categorized as locally advanced.

Once it spreads to other distant parts of the body, it is considered metastatic.

Cemiplimab was the first approved therapy in the United States for the treatment of locally advanced or metastatic CSCC and has subsequently been approved in the European Union and Australia.

Uveal Melanoma

Uveal melanoma, or UM, represents the predominant primary intraocular malignancy among adults, comprising over 95% of cases.

Globally, the estimated annual incidence of UM is approximately 4,800 individuals, with an estimated 1,700 new diagnoses occurring in the United States each year.

Risk factors for developing UM include fair skin, light-colored eyes, congenital ocular melanocytosis, melanocytoma, and the BAP1-tumour predisposition syndrome.

Despite effective local treatments for the primary tumor, nearly 50% of UM patients develop metastatic disease with liver being the most frequent (>90%) metastatic site.

Many UMs metastasize at a very early clinical stage, suggesting micrometastases are already present by the time the tumor is first recognized and treated.

Historically, 1-year survival rate of patients with distant metastases is 15%, while reported median survival time is less than 1 year ranging from 4 to 15 months.

Human capital

5 unchanged sentences

As such, we strive for, and are investing in, a work environment where our employees feel inspired and included.

We continue to focus on extending our diversity and inclusion initiatives across our entire global workforce.

We focus on identifying, attracting, retaining and developing highly talented and motivated employees.

Our equity and cash incentive plans are aligned to attract, retain and reward our employees through the granting of stock-based and cash-based compensation awards.

We conduct annual internal and external pay reviews to ensure fair and equitable pay for our employees, which includes an internal pay equity analysis, as well as the use of an external compensation analysis expert for the review of our employees' pay against external market data.

We believe motivating our employees to perform at their highest level and take pride in achieving company goals increases stockholder value.

The well-being, health and safety of our employees are integral to the success of our business.

Learning from and adapting to impacts from the COVID-19 outbreak, and in an ongoing effort to respect and protect the health and safety of our employees, we continue to monitor the pandemic's impact on office environments in general, assess our work-from-home, return-to-office, and other health and safety policies and, as applicable, follow local, state and federal guidelines.

We are committed to our employees’ health, safety and well-being.

Our work paradigm is flexible and designed to accommodate a range of work profiles.

Our workforce is a combination of full-time on-site, hybrid, and fully remote employees, including both at our manufacturing facility as well as in our offices in Woburn and the United Kingdom.

We offer a wide variety of competitive benefits to support our employees' physical, mental and financial well-being.

Our benefits package is comprehensive in coverage and offers options to support all employees in staying healthy, planning for their future and developing their careers.

Our management continues to assess and respond to the evolving needs of our workforce.

Corporate information

9 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business