Aptevo Therapeutics : 2024 Shareholder Letter

Le$er to Aptevo Shareholders

To My Fellow Shareholders,

As the annual mee6ng approaches, I want to take this 6me to reflect on where we are as a Company and where we expect to be at this 6me next year.

Over the last twelve months we focused heavily on advancing our clinical programs. Some of this was visible. For example, we released strong durability of remission data (DoR) from our APVO436 Phase 1b dose expansion trial. This data included one pa6ent who responded to treatment for eight cycles, the maximum allowed on protocol and three pa6ents who advanced to transplant from study. This is the best possible outcome for an AML pa6ent and the only possibility for a cure. The DoR data, together with already reported safety and efficacy data that significantly out-performs benchmarks from literature, supports our belief that APVO436 has significant poten6al to add to the standard-of-care and improve outcomes for AML pa6ents with limited exis6ng treatment op6ons.

Some of our work on APVO436 was not so visible. Upon the conclusion of the Phase 1b trial we worked closely with the FDA to determine the most effec6ve next steps to further derisk and differen6ate our therapy in the AML treatment space. While this work took 6me, this 6me was well spent and we now have a go forward strategy.

We concluded that a Phase 1b/2 trial in frontline AML pa6ents, conducted in two parts, was the best next step. The first part will be a Phase 1b dose op6miza6on, open label mul6-cohort study in combina6on with standard of care venetoclax + azaci6dine in venetoclax naïve pa6ents. We plan to ini6ate this part late in the second quarter. The trial will evaluate safety and efficacy independently and in rela6on to dose. This is to ensure that we iden6fy the point at which APVO436 provides the most clinical benefit with the lowest risk of side effects, in par6cular, Cytokine Release Syndrome (CRS), a serious and some6mes treatment-limi6ng adverse event.

Immune therapy as a category is characterized by high rates of CRS but APVO436 was designed to reduce cytokine release and reduce incidence of the syndrome. The great news is that APVO436 is performing in the clinic as we designed it and as it performed in the lab. In total, 90 pa6ents have been treated with APVO436 and only 27% experienced CRS. This is approximately one-third of the benchmark comparisons found in literature. Upon conclusion of the dose op6miza6on study, we plan to ini6ate a Phase 2 trial.

We are really excited about moving APVO436 forward. The data indicate that the compound holds significant promise for pa6ents figh6ng AML. It also demonstrates the power of our first proprietary pla`orm, ADAPTIR, to produce a powerful bispecific an6-cancer agent with a safety profile that reduces the risk of serious adverse events.

ALG.APV-527, our 4-1BB x 5T4 co-s6mulatory molecule is also in the clinic and being evaluated for the treatment of mul6ple solid tumor types likely to express 5T4. We ini6ated a Phase 1 open label, mul6-center,mul6-cohort dose escala6on trial last year. As of this communica6on the trial is more than 50% enrolled and dosing in cohort 5 (of 6) has been ini6ated.

We released early data from this trial in March. Exci6ngly, ALG.APV-527, like APVO436, is built with purpose: to overcome the safety challenges of first-genera6on4-1BB agonists by requiring the presence of 5T4 for ac6va6on and promote a targeted response that limits systemic exposure.

A highlight of our data is a breast cancer pa6ent who entered the trial and improved from progressive disease to long-las6ng stable disease (SD) while on therapy. The pa6ent has remained on study for more than nine months and been successfully transi6oned to a higher dose level, which may allow for increased clinical benefit. This is an uncommon occurrence in early solid tumor trials and even more uncommon because the pa6ent entered the trial with progressive disease.

A second heavily pretreated breast cancer pa6ent who was progressing prior to enrolling in the trial also sustained long las6ng stable disease and remained on study drug for seven months. Addi6onally, our analysis demonstrated measurable level of drug in circula6on (pharmacokine6c) and reproducible eleva6on of serum pharmacodynamic markers with dosing, sugges6ng the drug is biologically ac6ve. Biological ac6vity is a cri6cal point of analysis in early stage clinical trials.

It's important to remember that these are early days for this trial and for the development of ALG.APV-527 but outcomes such as those we have seen with the two breast cancer pa6ents, although anecdotal, are exci6ng and reinforce our belief that this solid-tumor directed an6- cancer agent has great poten6al, answering the ques6on "does it show up in the body in therapeu6cally meaningful quan66es?"

While our primary focus was, and con6nues to be, on our candidates in the clinic, we con6nue to progress the preclinical pipeline. Of par6cular interest is our newest pre-clinical candidate, APVO711. This is a dual mechanism checkpoint inhibitor with added func6onality that is also built for precision tumor targe6ng that limits systemic exposure. We recently released informa6on about our key learnings for this molecule, including:

• APVO711 imparts beneficial ajributes to both an6gen presen6ng cells and T cells that boost the immune response targeted at controlling tumor cells
• Experiments in cultured cells have confirmed that APVO711 enhances tumor cell killing by T cells
• In vivo studies have confirmed that APVO711 reduces the size of PD-L1-expressing tumors

The year was not without challenges. Microcap biotechnology companies con6nue to have difficulty accessing capital and Aptevo was no excep6on. We made difficult choices to accept capital under less than ideal terms. We did so to secure cri6cal funding that allows us to con6nue our work. We firmly believe our therapeu6cs have great poten6al to posi6vely impact the cancer treatment paradigm in AML and across a range of solid tumors. We believe the growing body of data released over the last two years demonstrates that poten6al and more recently released data further supports the story. So, while we raised money in a very difficult market, we did raise money and we con6nue to see results that demonstrate the poten6al of our assets for cancer pa6ents.

The cri6cal points to our story are that we are building differen6ated assets specifically designed for safety, precision tumor killing and combinability with standard of care. This last point is par6cularly important in cancer treatment today, where combina6on therapies dominate the standard of care across most cancer types.

In the year ahead, you can expect to hear from us across mul6ple fronts. In our APVO436 program we plan to ini6ate the dose op6miza6on trial this quarter and will report interim results by the end of the year. The ALG.APV-527 Phase 1b dose escala6on trial in solid tumors will be concluded by the end of the year and we plan to announce preliminary results. We will also ini6ate planning for the dose expansion part of the ALG.APV-527 trial, which will poten6ally be in combina6on therapy. We will con6nue to advance our preclinical pipeline, with emphasis on our unique and highly targeted molecule, APVO711, which demonstrates the flexibility of our pla`orm to evolve therapeu6cs relevant to the market.

I'll close here with a quote from Abraham Lincoln who said, "The best way to predict your future is to create it." Thank you for helping us create a world in which pa6ents with cancer have the poten6al to live longer, live stronger and live well.

Marvin White

President and CEO

Aptevo Therapeu6cs